Protein Ionizable Groups: pK Values and Their Contribution to Protein Stability and Solubility

Name: Work Video:
Duration: 3 min 30 s
C. Nick Pace; Gerald R. Grimsley; J. Martin Scholtz
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2886, 2979, 3007, 3116, 3350, 3360, 3454, 3463, 3889, 4135, 4205, 4303, 4343, 4568, 4693, 4703, 4801, 4923, 4975, 4981, 4992, 4998, 5019, 5174, 5197, 5225, 5231, 5242, 5272, 5281, 5302, 5315, 5338, 5345, 5360, 5374, 5379, 5387, 5460], 'pK': [28, 39, 52, 102, 113, 126, 208, 237, 252, 306, 475, 530, 550, 563, 600, 612, 640, 673, 727, 853, 855, 857, 898, 1035, 1120, 1198, 1307, 1427, 1509, 1540, 1554, 1563, 1567, 1577, 1582, 1597, 1636, 1698, 1735, 1817, 1834, 1977, 2051, 2239, 2437, 2445, 2477, 2619, 2853, 2874, 2890, 2945, 2949, 3014, 3074, 3087, 3099, 3111, 3124, 3174, 3181, 3188, 3212, 4109, 4113, 4202, 4310, 4355, 4367, 4490, 4967, 4972, 4989], 'values': [29, 40, 53, 103, 114, 127, 209, 238, 253, 307, 476, 564, 605, 613, 674, 689, 728, 838, 1036, 1428, 1510, 1541, 1583, 1598, 1637, 1699, 2240, 2446, 2620, 2767, 2946], 'ionizable': [32, 55, 106, 129, 212, 313, 479, 524, 543, 617, 716, 731, 737, 802, 1004, 1133, 1189, 1206, 1233, 1430, 1586, 1691, 1981, 2008, 2035, 2242, 2418, 2622, 2635, 2937, 4039, 4073, 4094, 4188], 'groups': [33, 56, 107, 130, 213, 256, 314, 425, 480, 509, 525, 544, 567, 665, 732, 806, 1008, 1190, 1234, 1250, 1272, 1280, 1284, 1393, 1431, 1587, 1640, 1721, 2046, 2117, 2243, 2419, 2623, 2636, 2801, 3225, 3359, 3521, 4040, 4342, 4447, 4624, 4687, 4791, 5079], 'how': [37, 111, 1891], 'these': [38, 112, 566, 1617, 1844, 2765, 2831, 3054, 4044, 4503], 'environment.': [44, 118], 'We': [45, 119], 'review': [46, 120, 1630], 'what': [47, 121, 561, 4577], 'has': [48, 122, 1832, 3010, 3743, 4308, 4353, 4365, 4513, 4615, 4970, 4987, 5454, 5544], 'been': [49, 123, 309, 2207, 4616], 'learned': [50, 124, 4580], 'about': [51, 125, 4581], 'from': [59, 133, 752, 840, 919, 1038, 1511, 1594, 1670, 1741, 1848, 2103, 2202, 2466, 3135, 3148, 5015, 5085, 5129, 5216, 5234, 5245], 'experimental': [60, 134, 159, 1627, 2510, 2647, 3984, 4913, 5273], 'studies': [61, 135, 2362, 3985, 5430], 'discuss': [63, 137], 'important': [65, 139, 465, 1194, 1415, 1608, 2835, 3451, 3888, 4047], 'contributions': [66, 140, 1416, 4048, 4498, 5508, 5527, 5558], 'they': [67, 141, 574, 621, 1255, 1897, 2939, 3246], 'make': [68, 142, 203, 1136, 1413, 3419, 4046, 4933, 5506, 5525, 5556], 'to': [69, 143, 202, 234, 301, 394, 434, 485, 559, 578, 596, 1299, 1348, 1417, 1665, 1672, 1748, 2086, 2204, 2468, 2666, 2707, 2820, 2900, 2936, 3023, 3089, 3101, 3113, 3171, 3191, 3250, 3423, 3452, 3466, 3477, 3657, 3696, 3795, 4049, 4067, 4106, 4166, 4193, 4210, 4249, 4253, 4296, 4319, 4487, 4499, 4587, 4746, 4851, 4937, 5008, 5099, 5194, 5199, 5257, 5270, 5406, 5414, 5509, 5513, 5528, 5532, 5559, 5573], 'protein': [70, 144, 418, 572, 1677, 1947, 1963, 2018, 2131, 2246, 2299, 2326, 2626, 2905, 3154, 3166, 3411, 3424, 3468, 3501, 3534, 3705, 3893, 4001, 4005, 4221, 4292, 4597, 4628, 4748, 4852, 4938, 4978, 4995, 5100, 5123, 5128, 5171, 5215, 5233, 5244, 5282, 5309, 5334, 5412, 5434, 5543, 5581], 'stability': [71, 145, 1419, 2709, 2902, 3268, 3412, 3469, 3542, 3660, 4006, 4053, 4251, 4321, 4501, 4515, 4569, 4589, 4593, 4606, 4749, 4853, 4939, 5010, 5101, 5259], 'solubility.': [73, 147, 5561], 'Sorensen': [148], 'defined': [149, 3940], 'pH': [150, 513, 1260, 1290, 1440, 1953, 2049, 2144, 2336, 3156, 3169, 3408, 4255, 5141, 5539], '1909': [152], '1917': [155], 'published': [156, 376], 'first': [158, 431], 'study': [160, 2251, 4914], 'titration': [163, 191, 2150], 'a': [165, 332, 417, 571, 897, 1119, 1127, 1667, 1676, 1728, 1833, 1946, 1962, 1979, 2094, 2124, 2141, 2245, 2250, 2301, 2324, 2330, 2353, 2770, 2852, 2904, 3011, 3070, 3264, 3420, 3455, 3500, 3528, 3704, 3732, 3739, 3892, 3922, 3925, 4000, 4060, 4246, 4309, 4316, 4354, 4366, 4489, 4514, 4572, 4855, 4916, 4928, 4934, 4957, 4971, 4988, 5135, 5200, 5268, 5300, 5411, 5424, 5493, 5545], 'protein,': [166, 2108, 3733, 3966, 4274, 4984], 'egg': [167], 'albumin': [168], '(1Sorensen': [169], 'S.P.L.': [170], 'Hoyrup': [171], 'M.': [172, 340, 2214, 2260, 2274, 2378, 2392, 2543, 2569, 2583, 2714, 2782, 3814, 4881, 5144], 'Hempel': [173], 'J.': [174, 452, 1496, 1780, 1874, 2169, 2283, 2401, 2592, 2684, 2914, 2990, 3040, 3322, 3592, 3714, 3777, 3830, 4076, 4078, 4081, 4230, 4378, 4409, 4550, 4631, 4633, 4636, 4660, 4709, 4711, 4714, 4763, 4884, 4901, 5442, 5593], 'Palitzsch': [175], 'S.': [176, 352, 942, 1160, 1365, 2266, 2272, 2384, 2390, 2575, 2581, 3276, 3709, 4015, 4394, 4535, 4898, 5150, 5152, 5158], 'C.': [177, 217, 402, 449], 'R.': [178, 403, 1399, 2158, 3283, 3394, 4833, 4900], 'Trav.': [179, 404], 'Lab.': [180, 405], 'Carlsberg.': [181, 406], '1917;': [182], '12:': [183], '68-163Google': [184], 'Scholar).': [185, 227, 298, 361, 410, 502, 660, 951, 996, 1169, 1229, 1374, 1411, 1479, 1506, 1658, 1793, 2227, 2293, 2411, 2557, 2694, 2728, 2796, 2965, 3000, 3050, 3210, 3296, 3404, 3445, 3519, 3652, 3691, 3790, 3847, 3883, 3918, 3982, 4032, 4091, 4240, 4336, 4419, 4560, 4679, 4724, 4782, 4843, 4911, 4954, 5072, 5119, 5169, 5452, 5603], 'In': [186, 228, 1579, 5550], 'succeeding': [187], 'years,': [188], 'hydrogen': [189, 710, 1319, 2822, 2844, 2849, 2933, 3021, 3055, 3064, 3081, 3093, 3106, 3121, 3192, 3215, 3243, 3485, 4213, 4281, 4454], 'ion': [190, 4794, 4817, 4823, 4847, 5046, 5223, 5251], 'curves': [192], 'were': [193, 392, 675, 1435, 1483, 1514, 1895, 2138, 2447, 2489, 2737, 2779, 3057, 3066, 5311], 'determined': [194, 310, 676, 1436, 2139], 'for': [195, 263, 311, 615, 724, 799, 846, 878, 885, 1001, 1061, 1086, 1107, 1173, 1204, 1429, 1989, 1997, 2414, 2538, 2657, 2751, 2759, 2775, 2843, 3059, 3223, 3228, 3342, 3668, 4502, 4571, 5569], 'several': [196, 2948, 3662, 5088], 'proteins,': [197, 1580, 2427, 3663, 4592], 'it': [199, 231, 243, 1805, 1824, 1852, 2561, 3339, 3742, 4102, 5286], 'was': [200, 232, 244, 375, 442, 641, 848, 1063, 1859, 2327, 2562, 2698, 2745, 3076, 3655, 3850, 4065, 4099, 4103, 4117, 5465, 5476, 5482, 5489, 5499], 'possible': [201, 233], 'rough': [204], 'estimates': [205], '(2Tanford': [216], 'Adv.': [218], 'Protein': [219, 324, 493, 651, 1048, 1073, 1522, 2180, 3395, 3510, 3554, 3643, 3682, 4834, 5265], 'Chem.': [220, 269, 454, 1450, 2916], '1962;': [221], '17:': [222, 496], '69-165Crossref': [223], 'Scopus': [224, 274, 358, 459, 499, 657, 948, 993, 1054, 1166, 1226, 1371, 1408, 1455, 1503, 1655, 1790, 1884, 2176, 2224, 2290, 2408, 2554, 2599, 2691, 2725, 2793, 2926, 2962, 2997, 3047, 3207, 3293, 3332, 3401, 3442, 3516, 3560, 3581, 3604, 3623, 3649, 3688, 3721, 3787, 3844, 3880, 3915, 3979, 4029, 4088, 4237, 4333, 4385, 4416, 4557, 4643, 4676, 4721, 4779, 4840, 4870, 4891, 4908, 4951, 5030, 5056, 5069, 5116, 5166, 5449, 5600], '(417)': [225], 'Google': [226, 276, 329, 360, 461, 501, 659, 950, 995, 1056, 1078, 1168, 1228, 1373, 1410, 1457, 1505, 1527, 1657, 1792, 1886, 2178, 2226, 2292, 2410, 2556, 2601, 2693, 2727, 2795, 2928, 2964, 2999, 3049, 3209, 3295, 3334, 3403, 3444, 3518, 3562, 3583, 3606, 3625, 3651, 3690, 3723, 3789, 3846, 3882, 3917, 3981, 4031, 4090, 4239, 4335, 4387, 4418, 4559, 4645, 4678, 4723, 4781, 4842, 4872, 4893, 4910, 4953, 5032, 5058, 5071, 5118, 5168, 5451, 5602], 'special': [229], 'cases,': [230], 'determine': [235, 474, 5400], 'groups,': [241, 2443, 2938], 'but': [242, 698, 2824, 3336, 3487, 3852, 4819, 5034, 5237], 'only': [245, 707, 1847, 4820, 5238], 'when': [246, 620, 1719, 2931, 3338, 4128, 4465, 4475, 5534], 'NMR': [247, 1446, 2361], 'became': [248], 'available': [249, 2655, 3195, 3667], 'that': [250, 413, 467, 473, 483, 510, 1295, 1311, 1900, 1924, 2112, 2146, 2305, 2364, 2516, 2520, 2533, 2610, 2828, 3301, 3366, 3414, 3523, 3746, 3758, 3886, 3987, 4279, 4585, 4618, 4728, 4734, 4743, 4927, 5093, 5250, 5372, 5500, 5565], 'could': [257, 2154], 'be': [258, 569, 701, 1287, 1589, 1619, 1694, 1707, 1717, 1987, 2020, 2101, 2155, 2432, 2818, 2834, 2876, 2892, 3218, 3489, 3895, 4125, 4191, 5195], 'readily': [259], 'determined,': [260], 'at': [261, 1259, 1289, 1950, 2047, 2089, 3069, 3155, 3167, 3427, 5104, 5140, 5538], 'least': [262, 775, 964, 1263, 5336, 5487], 'small': [264], '(3Markley': [266, 1447], 'J.L.': [267, 1448, 2677], 'Acc.': [268, 1449], 'Res.': [270, 1451, 3839], '1975;': [271, 1452], '8:': [272, 990, 1223, 1453, 3646, 4669, 4772], '70-80Crossref': [273, 1454], '(389)': [275, 1456], 'Scholar,': [277, 1057, 1458, 3563, 3584, 3607, 3626, 4388, 4646, 4873, 5059], '4Matthew': [278, 1459], 'J.B.': [279, 1460], 'Gurd': [280, 1461], 'F.R.': [281, 1462], 'Garcia-Moreno': [282, 1463, 1777, 1871, 2682, 3614], 'B.': [283, 1464, 2545, 2716, 2784, 3571, 3826, 4019, 4879], 'Flanagan': [284, 1465], 'M.A.': [285, 1466], 'March': [286, 1467], 'K.L.': [287, 1468, 2270, 2388, 2579, 2673, 3503, 3547, 3630, 3675, 4398, 4539], 'Shire': [288, 1469], 'S.J.': [289, 1470], 'Crit.': [290, 1471], 'Rev.': [291, 1472, 3872], 'Biochem.': [292, 1473, 4023], 'Mol.': [293, 1402, 1474, 1497, 2170, 2284, 2402, 2593, 2685, 2991, 3041, 3715, 3873, 4082, 4231, 4379, 4410, 4551, 4637, 4715, 4885, 4902, 5443, 5594], 'Biol.': [294, 1403, 1475, 1498, 2171, 2285, 2403, 2594, 2686, 2915, 2992, 3042, 3287, 3716, 3875, 4083, 4232, 4380, 4411, 4552, 4638, 4716, 4886, 4903, 5064, 5111, 5444, 5595], '1985;': [295, 1476], '18:': [296, 327, 1076, 1477, 1525], '91-197Google': [297, 1478], 'This': [299, 440, 908, 3132, 3474, 3653, 3848, 4164, 4241, 4561, 4600, 5002, 5170, 5248, 5367, 5463], 'led': [300, 2665], 'rapid': [302], 'progress,': [303], '>500': [305, 3812], 'have': [308, 2206, 2421, 3263, 3752, 3921, 4579], 'folded': [316, 1433, 1729, 3896, 3934, 4977, 4994], '(5Grimsley': [318, 1516], 'G.R.': [319, 646, 1043, 1068, 1491, 1517, 2268, 2386, 2577, 2985, 3035, 3628, 4225, 4373], 'Scholtz': [320, 647, 1044, 1069, 1492, 1518, 2279, 2397, 2588, 2908, 2986, 3036, 3279, 3639, 3710, 4226, 4374, 4405, 4546, 5438, 5589], 'J.M.': [321, 648, 1045, 1070, 1359, 1493, 1519, 2276, 2278, 2280, 2394, 2396, 2398, 2585, 2587, 2589, 2909, 2987, 3037, 3280, 3609, 3640, 3711, 4227, 4375, 4406, 4547, 5439, 5590], 'Pace': [322, 649, 1046, 1071, 1494, 1520, 2281, 2399, 2590, 2912, 2988, 3038, 3641, 3712, 4228, 4376, 4407, 4548, 5440, 5591], 'C.N.': [323, 650, 1047, 1072, 1495, 1521, 2282, 2400, 2591, 2913, 2989, 3039, 3274, 3432, 3642, 3713, 4229, 4377, 4408, 4549, 5061, 5108, 5441, 5592], 'Sci.': [325, 350, 494, 652, 1049, 1074, 1363, 1523, 3288, 3396, 3511, 3555, 3644, 3683, 4835], '2009;': [326, 1075, 1524], '247-251PubMed': [328, 1077, 1526], 'Scholar)': [330, 462, 1887, 2602, 2929, 3335, 4894], 'more': [333, 2861, 3377, 4435, 5077, 5288], 'limited': [334], 'number': [335, 1482, 3456, 3808, 4070, 4620, 4683, 5221], 'unfolded': [337, 3305, 3750, 3898, 3937, 4983, 5000], '(6Tollinger': [339], 'Crowhurst': [341], 'K.A.': [342], 'Kay': [343], 'L.E.': [344], 'Forman-Kay': [345], 'J.D.': [346], 'Proc.': [347, 1360], 'Natl.': [348, 1361], 'Acad.': [349, 1362], 'U.': [351, 1364, 4662, 4765], 'A.': [353, 1366, 2166, 2210, 2547, 2718, 2786, 3505, 3549, 3677, 3824, 4664, 4767, 4875], '2003;': [354, 1367, 2286, 2404, 2595, 2917, 3619], '100:': [355, 1368], '4545-4550Crossref': [356], 'PubMed': [357, 498, 656, 947, 992, 1053, 1165, 1225, 1370, 1407, 1502, 1654, 1789, 1883, 2175, 2223, 2289, 2407, 2553, 2598, 2690, 2724, 2792, 2925, 2961, 2996, 3046, 3206, 3292, 3331, 3400, 3441, 3515, 3559, 3580, 3603, 3622, 3648, 3687, 3720, 3786, 3843, 3879, 3914, 3978, 4028, 4087, 4236, 4332, 4384, 4415, 4556, 4642, 4720, 4839, 4869, 4890, 4907, 4950, 5029, 5055, 5068, 5115, 5165, 5448, 5599], '(80)': [359], 'landmark': [363], 'paper': [364, 466], 'by': [365, 396, 444, 585, 703, 709, 790, 980, 1386, 1437, 1561, 1575, 1599, 1911, 1928, 2249, 2645, 2947, 2970, 3179, 3470, 3479, 3491, 3543, 3942, 4111, 4130, 4212, 4806, 5313], 'Debye': [366], 'Hückel': [368, 381], 'theory': [371], 'electrolyte': [373], 'solutions': [374], '1923': [378], '(7Debye': [379], 'P.': [380, 1397, 3310, 3765, 3828, 5209], 'E.': [382, 3278, 5156], 'Phys.': [383], 'Z.': [384, 3316, 3771, 3834], '1923;': [385], '24:': [386], '185-206Google': [387], 'Scholar),': [388, 1528, 5033], 'ideas': [391], 'extended': [393, 443], 'Linderstrom-Lang': [397], '1924': [399], '(8Linderstrom-Lang': [400], 'K.U.': [401], '1924;': [407], '15:': [408, 654, 1051], '1-29Google': [409], 'He': [411], 'recognized': [412], 'would': [419, 568, 1853, 4123, 4469, 4479], 'influence': [420, 3994, 4003], 'incorporated': [427], 'this': [428, 1341, 1763, 2083, 3176, 4139, 4524, 4963, 5191], 'into': [429, 5433], 'model': [432, 441], 'developed': [433], 'understand': [435], 'acid/base': [436], 'properties': [437], 'proteins.': [439, 1423, 3805, 4055, 4197, 5264], 'Tanford': [445], 'Kirkwood': [447, 450], '(9Tanford': [448], 'J.G.': [451], 'Am.': [453], 'Soc.': [455, 3284], '1957;': [456], '79:': [457], '5333-5339Crossref': [458], '(735)': [460], 'an': [464, 469, 785, 975, 1301, 1760, 2297, 2471, 2667, 4276], 'triggered': [468], 'interest': [470, 3462], 'factors': [472, 3885, 4485], 'continues': [484], 'present': [487, 623, 893, 1115], 'day': [488], '(10Spassov': [489], 'V.Z.': [490, 3390, 4829], 'Yan': [491], 'L.': [492, 2168, 4656, 4759, 4877], '2008;': [495, 2687, 4025, 5162], '1955-1970Crossref': [497], '(110)': [500], 'Seven': [503], 'amino': [504, 635, 747, 768, 824, 914, 957, 1026, 1143, 1279, 1830, 3471, 5471], 'acid': [505, 636, 748, 769, 915, 958, 1738, 3472], 'side': [506, 618, 638, 738, 1134, 1210, 1314, 1345, 1377, 1391, 1571, 3002, 3025, 3530, 4732, 5458], 'chains': [507, 619, 739, 1135, 1378, 3026, 4733], 'contain': [508, 5076], 'ionize': [511], 'between': [512, 2066, 2098, 2115, 2507, 3933, 4786, 4919, 5208, 5385, 5395], '1': [514, 609, 1216], '14.': [516], 'For': [517, 537, 763, 952, 1551, 2439, 4092, 4680], 'Asp,': [518, 1701, 1809, 1990, 4180], 'Glu,': [519, 810, 1012, 1276, 1702, 1991, 4182], 'Tyr,': [520, 822, 1024, 1992], 'Cys,': [522, 818, 1020, 1239, 1703], 'uncharged': [527, 552, 1258], 'below': [528, 548, 1547], 'negatively': [532], 'charged': [533, 547, 1288, 1668, 4623, 4686, 4731, 4790, 5078, 5425], 'above': [534, 553, 1545, 1967, 2485, 3129], 'pK.': [536, 555, 4482], 'His,': [538, 814, 1016, 1243, 1712, 1998, 5501], 'Lys,': [539, 827, 1029, 1713, 1828, 1999], 'Arg,': [541, 1269, 4178], 'positively': [546], 'It': [556, 1292, 1858, 2512, 3297, 4614, 4725], 'is': [557, 633, 742, 770, 777, 782, 798, 876, 909, 959, 966, 972, 1000, 1084, 1175, 1193, 1212, 1293, 1297, 1327, 1559, 1573, 1662, 1683, 1739, 1795, 1806, 1825, 1909, 1925, 1948, 1964, 1973, 2030, 2040, 2057, 2063, 2084, 2132, 2247, 2296, 2343, 2351, 2513, 2526, 2629, 2773, 2968, 3125, 3145, 3194, 3298, 3340, 3376, 3386, 3460, 3475, 3695, 3810, 3939, 4176, 4208, 4266, 4306, 4349, 4361, 4423, 4432, 4448, 4463, 4562, 4601, 4610, 4688, 4740, 4854, 5040, 5125, 5172, 5192, 5219, 5240, 5267, 5299, 5335, 5368, 5413, 5536, 5572], 'useful': [558], 'know': [560], 'if': [573, 3053], 'completely': [576], 'exposed': [577, 5457], 'solvent,': [579], 'not': [580, 583, 700, 1926, 2514, 2837, 3418, 4602, 4736], 'hydrogen-bonded,': [581, 1382], 'affected': [584], 'presence': [587], 'any': [589], 'formal': [590], 'charges.': [591, 2069], 'These': [592, 687, 1249, 1283, 2641, 2815, 3791, 4121, 4186, 4483, 5562], 'generally': [594, 1257, 1286, 2841, 2896, 3363, 3920, 4124, 5075, 5404], 'referred': [595, 2819, 3794], 'as': [597, 721, 2129, 2140, 2455, 2483, 2821, 3219, 3221, 3726, 3796, 4119, 4134, 4596, 5296, 5348, 5350, 5391, 5393], 'intrinsic': [599, 1596], '(pKint)': [601], 'values.': [602, 1199, 1550, 2496, 2511], 'pKint': [604, 688, 1549], 'given': [606, 683, 877, 1085, 1176, 1213, 1980, 5333], 'Table': [608, 685, 1178, 1215, 1535, 1603, 4136], 'observed': [614, 2156, 4570], 'blocked': [625], 'pentapeptides': [626, 679, 836], 'with': [627, 1132, 1388, 1626, 1808, 1827, 1930, 1933, 2022, 2300, 2320, 2329, 2470, 2486, 2493, 2747, 2805, 2863, 2879, 3671, 4290, 4627, 4695, 4705, 4960, 5134, 5423, 5467, 5583], 'structure': [629, 2105], 'Ala-Ala-X-Ala-Ala,': [630], 'where': [631, 1678, 2028, 2630, 3951, 5541], 'X': [632], 'whose': [637], 'chain': [639, 1211, 1315, 1346, 1392, 1572, 3003, 3531, 3757, 5459], 'measured': [642, 1484, 2495, 4129, 5537], '(11Thurlkill': [643], 'R.L.': [644, 1041, 1489, 2262, 2380, 2571, 2983, 3033, 3638, 4223, 4371, 4396, 4537], 'Grimsley': [645, 1042, 1490, 2267, 2385, 2576, 2984, 3034, 4224, 4372], '2006;': [653, 1050, 1499, 2220, 2993, 3043, 3600, 4233, 4381], '1214-1218Crossref': [655, 1052], '(265)': [658, 1055], 'α-carboxyl': [662], 'α-amino': [664], 'can': [668, 1316, 2019, 2100, 2802, 2833, 2940, 3217, 3488, 3536, 3730, 3737, 3860, 3993, 4190, 4932], 'also': [669, 682, 2803, 4314], 'ionize,': [670], 'similar': [678, 2372, 2422], '1.': [686, 1179, 1536, 1614, 4137], 'reflect': [690], 'inductive': [692], 'effects': [693, 1601, 1609, 2706], 'neighboring': [695, 2812], 'peptide': [696], 'bonds': [697, 2895, 2934, 3022, 3056, 3065, 3082, 3094, 3107, 3486], 'will': [699, 1285, 1618, 1693, 1706, 1716, 1986, 2190, 2420, 2431, 2817, 2854, 2875, 2891, 3894, 5102], 'influenced': [702], 'charge-charge': [704, 2611, 3494, 3728, 3735, 4809, 5042], 'interactions': [705, 1929, 2236, 2430, 2612, 2661, 2736, 2816, 2832, 2859, 3368, 3416, 3449, 3495, 3539, 3729, 3736, 3992, 4285, 4785, 4800, 5043], 'minimally': [708], 'bonding': [711, 2850, 3159, 3193, 4214, 4282], 'or': [712, 1592, 1725, 1932, 2809, 2878, 2942, 3483, 3751, 3897, 3929, 4195, 4738, 4796, 5426, 5585], 'burial': [713, 1186, 1203, 4729], 'group.': [717], 'They': [718, 1412], 'should': [719, 4594], 'serve': [720], 'good': [722, 2229, 2491, 3693], 'models': [723], 'unperturbed': [726], 'proteins.TABLE': [734], '1Characteristics': [735], 'proteinsGroupContentaThis': [741], 'current': [744, 911], 'average': [745, 912, 1171, 1201, 2472, 3086, 3098], '%': [746, 780, 796, 913, 970, 998, 1202], 'content': [749, 916, 1172], 'all': [753, 920, 1898, 3104], 'three': [754, 921, 1606, 3019, 3105, 4452], 'domains': [755, 922], 'life:': [757, 924], 'Bacteria,': [758, 925], 'Archaea,': [759, 926], 'Eukaryota': [761, 928], '(12).': [762], 'comparison,': [764, 953], 'most': [766, 955, 1231, 1331, 1607, 3260, 3428, 4339, 5038, 5121, 5205, 5262, 5417, 5456, 5479, 5576], 'abundant': [767, 776, 956, 965], 'Leu': [771, 960], '(10.3%),': [772, 961], 'Trp': [778, 967], '(1.1%).BuriedbThe': [779], 'buried': [781, 797, 971, 999, 1232, 1253, 1264, 1298, 1796, 1922, 3146, 4072, 4127, 4168, 4187, 4242, 4340, 4351, 4363, 4622, 4685, 4929], 'based': [783, 973], 'analysis': [786, 976, 2653, 2697, 4277], '61': [788, 978], 'Lesser': [791, 981], 'Rose': [793, 983, 986, 1219], '(13).': [794], 'just': [800, 1002, 3248, 3270], 'group:': [803, 1005], 'carboxyl': [805, 891, 1007, 1113, 1570, 1811, 2975, 3004, 3141, 3177, 3224, 4243, 4288, 4341, 4446, 4505], 'Asp': [808, 847, 1010, 1062, 1274, 2313, 4149, 5552, 5584], 'imidazole': [812, 1014, 1241], '–SH': [816, 1018, 1237], '–OH': [820, 1022, 1246], 'group': [825, 892, 1027, 1114, 1207, 1326, 1558, 1669, 1692, 1812, 1831, 1919, 2009, 2036, 2976, 3142, 3178, 4244, 4289], 'guanidinium': [830, 1032, 1267, 1325], 'Arg.pK': [832], 'value': [833, 845, 873, 1060, 1081, 1906, 2187, 2498, 2519, 2532, 4110], 'alanine': [835], '(pKint)cpK': [837], 'Ref.': [841, 851, 881, 1039, 1066, 1089], '11,': [842], 'corrected': [849, 1064], '5.Average': [852], 'valueLow': [854], 'valueHigh': [856], 'valueNo.': [858], 'measurements%%Asp5.2563.93.5': [860], '±': [861, 863, 865, 867, 869, 871, 903, 906], '1.20.59.2139Glu6.5484.34.2': [862], '0.92.18.8153His2.2726.56.6': [864], '1.02.49.2131Cys1.2908.66.8': [866], '2.72.511.125Tyr3.2679.810.3': [868], '1.26.112.120Lys5.93410.410.5': [870], '1.15.712.135Arg5.15612.3dA': [872], '12.48': [875, 1083], 'Arg': [879, 895, 1087, 1117, 1296, 1313, 1344, 1376, 1715, 4144, 5522], '49.': [882], 'A': [883, 1080, 1105, 1480, 2228, 2497, 2651, 2695, 3183], 'correction': [884, 1106], 'negative': [887, 1109, 3150], 'gives': [896, 1118], '≈': [900, 1122], '12.3.C': [901], 'terminus3.73.3': [902], '0.82.45.922N': [904], 'terminus8.07.7': [905], '0.56.89.116a': [907], '(12Jordan': [929, 1147], 'I.K.': [930, 1148], 'Kondrashov': [931, 939, 1149, 1157], 'F.A.': [932, 1150], 'Adzhubei': [933, 1151], 'I.A.': [934, 1152], 'Wolf': [935, 1153], 'Y.I.': [936, 1154], 'Koonin': [937, 1155], 'E.V.': [938, 1156], 'A.S.': [940, 1158], 'Sunyaev': [941, 1159], 'Nature.': [943, 1161], '2005;': [944, 1162, 2958, 3203, 3876, 4084, 4412, 4553, 4639, 4717], '433:': [945, 1163], '633-638Crossref': [946, 1164], '(206)': [949, 1167], '(1.1%).b': [968], '(13Lesser': [984, 1217], 'G.J.': [985, 1218, 1648], 'G.D.': [987, 1220], 'Proteins.': [988, 1221, 2957, 3202, 3910, 3974], '1990;': [989, 1222, 3438, 4329, 4866, 4887, 4947], '6-13Crossref': [991, 1224], '(147)': [994, 1227], 'Arg.c': [1034], '11Thurlkill': [1040], '5Grimsley': [1067], 'Scholar.d': [1079], '49Cohn': [1090], 'E.J.': [1091, 5318], 'Edsall': [1092, 5319], 'J.T.': [1093, 5320], 'Proteins,': [1094, 5321], 'Amino': [1095, 1130, 5322], 'Acids': [1096, 3838, 5323], 'Peptides.': [1098, 5325], 'Hafner': [1099, 5326], 'Publishing': [1100, 5327], 'Co.,': [1101, 5328], 'New': [1102, 5329], 'York1943Google': [1103, 5330], 'Scholar.': [1104], '12.3.': [1123], 'Open': [1124], 'table': [1125], 'new': [1128, 3857], 'tab': [1129], 'acids': [1131, 1144], 'up,': [1137], 'average,': [1139, 4812], '29%': [1140], 'each': [1174, 1209, 4093], 'As': [1180, 4299], 'discussed': [1181, 1620, 2780, 4036, 4300], 'below,': [1182, 4301], 'extent': [1184, 1302], 'determining': [1196, 3890], 'Tyr.': [1248], 'often': [1252, 4045, 5039], 'because': [1254, 1303, 1336, 2457, 3139], '7.': [1261, 1291], 'carboxylate': [1271], 'Lys.': [1282, 4185], 'surprising': [1294, 2515, 5497], 'such': [1300], 'high': [1306, 3220, 3926], 'fact': [1310], 'donate': [1317], 'five': [1318], 'bonds.': [1320, 2845], 'However,': [1321, 3373], 'water,': [1323, 2078], 'one': [1328, 1556, 1569, 3068, 4563, 4741, 4821, 5239], 'weakly': [1332], 'hydrated': [1333], 'cations,': [1334], 'probably': [1335, 3426], 'delocalization,': [1339], 'makes': [1342, 4245, 4315, 5285], 'easier': [1347], 'bury': [1349], '(14Mason': [1350], 'P.E.': [1351, 3870], 'Neilson': [1352], 'G.W.': [1353], 'Dempsey': [1354], 'C.E.': [1355], 'Barnes': [1356], 'A.C.': [1357], 'Cruickshank': [1358], '4557-4561Crossref': [1369], '(293)': [1372], 'Buried': [1375, 4033], 'charged,': [1380, 2973], 'extensively': [1381], 'frequently': [1384], 'interact': [1385, 2804], 'stacking': [1387], 'other': [1389, 2013, 2045, 2646, 3672, 4284, 5469], 'planar': [1390], '(15Chakrabarti': [1396], 'Bhattacharyya': [1398], 'Prog.': [1400], 'Biophys.': [1401, 1779, 1873, 2218, 3321, 3776, 4024], '2007;': [1404, 1781, 1875, 2550, 2721, 2789, 3323, 3512, 3556, 3577, 3684, 3717, 3778, 3840, 5445, 5596], '95:': [1405], '83-137Crossref': [1406], '(148)': [1409], 'many': [1414, 3302, 3747, 4038, 5291], 'Most': [1424], 'measuring': [1438], 'dependence': [1441, 3409, 4256], 'chemical': [1443], 'shifts': [1444, 3189], 'using': [1445, 1485], 'smaller': [1481], 'indirect': [1486], 'techniques': [1487], '(16Thurlkill': [1488, 2982, 3032, 4222, 4370], '362:': [1500, 2994, 3044, 4234, 4382], '594-604Crossref': [1501, 2995, 3045, 4235, 4383], '(56)': [1504, 2998, 3048, 4238, 4386], 'Recently,': [1507, 3741], '541': [1508], '78': [1512], 'compiled': [1515], 'results': [1531, 2537, 2607, 3134, 5563], 'summarized': [1533, 1611, 5312], 'Many': [1537], 'perturbed': [1543], 'far': [1544], 'example,': [1552, 4681], 'sulfhydryl': [1557, 3229], 'lowered': [1560, 1593, 1718, 4209], '>6': [1562], 'units,': [1564, 4114], 'raised': [1574, 1591, 1708], '>5': [1576, 4112], 'units.': [1578, 2357, 3182], 'may': [1588, 2118, 2127], 'substantially': [1590, 4626, 4964], 'environment': [1600, 4442], '(see': [1602], '1).': [1604], 'Fig.': [1613], 'Each': [1615], 'general': [1622], 'terms': [1623], 'illustrated': [1625], 'results.': [1628], 'Another': [1629], 'discusses': [1631], 'perturbation': [1633], 'catalytic': [1639], 'enzyme': [1642], 'active': [1643], 'sites': [1644], '(17Harris': [1645], 'T.K.': [1646], 'Turner': [1647], 'IUBMB': [1649], 'Life.': [1650], '2002;': [1651], '53:': [1652], '85-98Crossref': [1653], '(384)': [1656], 'Dehydration': [1659], '(Born': [1660], 'Effect)—It': [1661], 'energetically': [1663], 'unfavorable': [1664, 3388, 3990, 5507, 5526], 'transfer': [1666], 'water': [1671, 1744], 'interior': [1674], 'dielectric': [1680, 2059], 'constant': [1681], '(ϵprotein)': [1682], 'lower.': [1684], 'neutral': [1687, 5354], 'favored,': [1695], 'Tyr': [1705], 'those': [1710, 5371, 5394], 'buried,': [1723, 2972, 4042, 4200, 4307], 'partially': [1724], 'completely,': [1726], 'protein.': [1730, 3740, 4440, 5001], 'To': [1731, 3051], 'illustrate': [1732], 'this,': [1733, 2560, 3347, 3447], 'acetic': [1737], 'increased': [1740], '4.8': [1742], '(ϵ': [1745, 1752], '=': [1746, 1753, 1856, 2026, 2050, 2501, 2749, 2757, 3947], '78)': [1747], '10.1': [1749], 'ethanol': [1751], '24).': [1754], 'Studies': [1755, 3405], 'staphylococcal': [1757], 'nuclease': [1758, 2664], 'provide': [1759, 5431], 'example': [1761, 2230, 2967], 'effect': [1764, 2148, 2233, 2541, 2733, 2754, 2778, 2847, 3138, 3241], '(18Karp': [1767, 1861], 'D.A.': [1768, 1862], 'Gittis': [1769, 1863], 'A.G.': [1770, 1864], 'Stahley': [1771, 1865], 'M.R.': [1772, 1866, 4080, 4635, 4713], 'Fitch': [1773, 1867, 2678, 3610], 'C.A.': [1774, 1868, 2679, 3611], 'Stites': [1775, 1869, 3616], 'W.E.': [1776, 1870, 3617], 'E.B.': [1778, 1872, 3615], '92:': [1782, 1876, 3324, 3779], '2041-2053Abstract': [1783, 1877], 'Full': [1784, 1786, 1878, 1880, 2920, 2922, 3326, 3328, 3781, 3783, 4671, 4673, 4774, 4776], 'Text': [1785, 1787, 1879, 1881, 2921, 2923, 3327, 3329, 3782, 3784, 4672, 4674, 4775, 4777], 'PDF': [1788, 1882, 2924, 3330, 3785, 4675, 4778], '(122)': [1791, 1885], 'Val-66': [1794], 'hydrophobic': [1799, 3240, 3481, 5418, 5577], 'core': [1800], 'enzyme.': [1803], 'When': [1804, 1823, 2729, 3079, 3091, 3103], 'replaced': [1807, 1826, 5466], 'hasapK': [1813], '8.9,': [1815], '5': [1816, 2321, 4493], 'units': [1818, 1838, 2950, 3128, 4494], 'higher': [1819, 2449, 2528, 3227, 5105], 'than': [1820, 1840, 2452, 2529, 3382, 4271, 4437, 4519, 5083], 'pKint.': [1822, 1842, 3131], '5.5,': [1836], '4.9': [1837], 'lower': [1839, 2943, 3172, 4470, 4747], 'If': [1843, 4101], 'changes': [1845], 'resulted': [1846], 'Born': [1850, 2540, 2732, 2753, 2777, 3137], 'effect,': [1851], 'require': [1854], 'ϵprotein': [1855], '7.2.': [1857], 'concluded': [1860, 2563], 'that,': [1888, 2603], '"Regardless': [1889], 'pKa': [1893, 1905], 'calculations': [1894], 'performed,': [1896], 'showed': [1899, 3522, 4926], 'shift': [1902, 3213, 4107], 'Asp-66': [1908], 'governed': [1910], 'loss': [1913], 'hydration': [1915], 'carboxylic': [1918], 'offset': [1927], 'charges': [1931, 2014, 2072, 2099, 2195, 2808, 3370], 'polar': [1934, 2813, 5427], 'atoms': [1935], 'protein."': [1938], 'Charge-Charge': [1939, 3357], 'Interactions': [1940, 2798], '(Coulombic': [1941], 'Interactions)—The': [1942], 'zero': [1949], 'isoelectric': [1952, 5343], '(pI).': [1954], 'Below': [1955], 'pI,': [1957, 1969], 'positive,': [1965], 'negative.': [1974], 'At': [1975, 2335], 'group,': [1982, 2055, 2869, 2885, 4095], '–½': [1988], 'Cys': [1994], '+½': [1996], 'Arg.': [2001], 'energy': [2003], 'interaction': [2005], '(i)': [2010], '(j)': [2015], 'calculated': [2021, 2102, 2482, 2508], "Coulomb's": [2023, 2487], 'law:': [2024], 'ΔGij': [2025], '∑qiqj/ϵrij,': [2027], 'qi': [2029], 'interest,': [2038], 'qj': [2039], 'ionizing': [2054], 'ϵ': [2056, 2189, 2200, 2500, 2518, 2531, 2669, 2748, 2756, 2766, 2772], 'constant,': [2060], 'rij': [2062], 'distance': [2065, 2097, 2114], 'two': [2068, 2194, 2426, 3092, 4338, 4445, 4504], '(When': [2070], 'opposite': [2071], '4.2': [2074], 'Å': [2075], 'apart': [2076], 'ΔG': [2079], '=–l': [2080], 'kcal/mol,': [2081], 'reduced': [2085], '–0.5': [2087], 'kcal/mol': [2088, 2899, 3272, 3353, 3430, 3545, 4268, 4295, 4425, 4434, 4517, 5007], 'ionic': [2091], 'strength': [2092], 'inside': [2093], 'cell.)': [2095], 'keeping': [2109], 'mind': [2111, 2827], 'differ': [2119], 'solution': [2121], 'crystal': [2125], 'vary': [2128], 'titrated.': [2133], '(For': [2134], 'RNase': [2135, 2253, 2294, 2980, 3008, 4206, 4264, 4344, 4511, 5461, 5519], 'A,': [2136], 'structures': [2137, 2359, 2366], 'so': [2145, 2184, 3259, 3365, 3670], 'distances': [2153], '(19Berisio': [2157], 'Lamzin': [2159], 'V.S.': [2160], 'Sica': [2161], 'F.': [2162], 'Wilson': [2163], 'K.S.': [2164], 'Zagari': [2165], 'Mazzarella': [2167], '1999;': [2172, 3645, 4904], '292:': [2173], '845-854Crossref': [2174], '(77)': [2177], 'Scholar).)': [2179, 3724], 'interiors': [2181], 'heterogeneous,': [2183], 'effective': [2186, 2668], 'which': [2193, 2628, 2871, 2887, 4348, 4360, 4468, 4478], 'considered.': [2197], 'Values': [2198], 'ranging': [2201], '2': [2203], '80': [2205], 'used': [2208, 2842, 3656, 3800, 4066, 4192, 5037, 5295, 5405], '(20Warshel': [2209], 'Sharma': [2211], 'P.K.': [2212], 'Kato': [2213], 'Parson': [2215], 'W.W.': [2216], 'Biochim.': [2217], 'Acta.': [2219], '1764:': [2221], '1647-1676Crossref': [2222], '(449)': [2225], 'coulombic': [2235, 2429, 2660, 2735, 2760, 3367, 3415, 3448, 3538, 3991], 'provided': [2248, 2969], 'Sa': [2254, 2295, 4345, 4512], '(21Laurents': [2255, 2373, 2564], 'D.V.': [2256, 2374, 2565, 3434], 'Huyghues-Despointes': [2257, 2375, 2566, 3635], 'B.M.': [2258, 2376, 2567, 3636], 'Bruix': [2259, 2377, 2568], 'Thurlkill': [2261, 2379, 2570, 3637, 4395, 4536], 'Schell': [2263, 2381, 2572, 4661, 4764], 'D.': [2264, 2382, 2573], 'Newsom': [2265, 2383, 2574, 4393, 4534], 'Shaw': [2269, 2387, 2578, 3629, 4397, 4538], 'Trevino': [2271, 2389, 2580, 3275], 'Rico': [2273, 2391, 2582], 'Briggs': [2275, 2393, 2584], 'Antosiewicz': [2277, 2395, 2586], '325:': [2287, 2405, 2596], '1077-1092Crossref': [2288, 2406, 2597], '(90)': [2291, 2409, 2600], 'acidic': [2298], 'pI': [2302, 2331, 5517], '3.5': [2304], 'contains': [2306], 'no': [2307], 'Lys': [2308, 2322, 4160, 5524], 'residues': [2309, 2316, 4074, 4122, 4161, 4169, 4189, 4692, 4697, 4702, 4707, 4827], '(0K).': [2310], 'By': [2311], 'replacing': [2312], 'Glu': [2315, 4154], 'surface': [2319, 3482, 3498, 3535, 3702, 4132, 5422, 5582], 'residues,': [2323, 4145, 4150, 4155, 4172], 'basic': [2325], 'created': [2328], '10.2': [2333], '(5K).': [2334], '7,': [2337, 5540], '0K': [2342, 2368], '–7,': [2344], '5K': [2350, 2370, 2451], '+3,': [2352], 'difference': [2354, 2473, 4062, 4491, 5207], '∼10': [2356], 'Crystal': [2358], 'show': [2363, 3413, 3986], 'except': [2413], 'charge,': [2416, 3928], 'environments': [2423], 'main': [2434], 'determinant': [2435], 'differences.': [2438], '11': [2441], 'common': [2442, 5201], 'always': [2448, 5555], '0K,': [2454], 'expected': [2456], 'greater': [2460, 4518], 'positive': [2461, 3162, 4217], 'charge.': [2462], 'differences': [2464, 2478], 'ranged': [2465], '0.03': [2467], '2.19,': [2469], '0.75.': [2475], '(pK0K': [2479], '–': [2480, 3949], 'pK5K)': [2481], 'described': [2484], 'law': [2488], 'agreement': [2492, 2506, 2524, 2744], '45': [2502], 'gave': [2503, 2521, 2534], 'best': [2505, 2523, 2536, 2743, 5567], 'here': [2525], 'considerably': [2527], '(22Roca': [2542, 2713, 2781], 'Messer': [2544, 2715, 2783], 'Warshel': [2546, 2717, 2785], 'FEBS': [2548, 2719, 2787], 'Lett.': [2549, 2720, 2788], '581:': [2551, 2722, 2790], '2065-2071Crossref': [2552, 2723, 2791], '(43)': [2555, 2726, 2794], 'Based': [2558, 4575], '"Taken': [2604], 'together,': [2605], 'evidence': [2609, 5091], 'chief': [2615], 'perturbant': [2616], 'surface,': [2627], 'majority': [2632], 'positioned': [2638], 'proteins."': [2640], 'conclusions': [2642], 'supported': [2644], 'theoretical': [2649, 2696], 'studies.': [2650], 'global': [2652], 'data': [2656], 'short-to-long': [2658], 'range': [2659, 3354], 'staphylococcus': [2663], '≈42': [2671], '(23Baran': [2672], 'Chimenti': [2674], 'M.S.': [2675, 3822], 'Schlessman': [2676], 'Herbst': [2680], 'K.J.': [2681], 'B.E.': [2683], '379:': [2688], '1045-1062Crossref': [2689], '(42)': [2692], 'successful': [2699], 'predicting': [2701], 'contribution': [2703, 3422, 4248, 4318, 4936, 5095], 'electrostatic': [2705], 'four': [2711, 4815], 'both': [2730, 4004], 'included': [2738], 'analysis,': [2741], 'found': [2746, 5173, 5230, 5241], '20–80': [2750], '40': [2758], 'interactions.': [2761], 'significance': [2763], 'why': [2769], 'large': [2771, 3421, 4247, 4317], 'needed': [2774], 'Charge-Dipole': [2797], '(Hydrogen': [2799], 'Bonds)—Ionizable': [2800], 'partial': [2807], 'dipoles': [2810], 'groups.': [2814, 3230, 4506], 'bonds,': [2823, 3122, 4455], 'keep': [2825], 'some': [2829, 3380, 3862], 'meet': [2838], 'definitions': [2840], 'whether': [2857, 3891], 'favorable': [2862, 3378, 3988, 4805, 4935, 5557], 'protonated': [2865], 'case': [2872, 2888], 'raised,': [2877], 'deprotonated': [2881], 'lowered.': [2893], 'Hydrogen': [2894, 3158], 'contribute': [2897, 4293, 4586, 4849], '1–2': [2898], '(24Takano': [2906], 'K.': [2907, 4392, 4533, 5148, 5160], 'Sacchettini': [2910, 4403, 4544], 'J.C.': [2911, 4017, 4404, 4545], '278:': [2918], '31790-31795Abstract': [2919], '(55)': [2927], 'and,': [2930], 'raise': [2941, 4480], '(25Li': [2951, 3196], 'H.': [2952, 3197, 3573, 5146], 'Robertson': [2953, 3198], 'A.D.': [2954, 3199, 3392, 4831], 'Jensen': [2955, 3200], 'J.H.': [2956, 3201, 3567, 4013], '61:': [2959, 3204], '704-721Crossref': [2960, 3205], '(1629)': [2963, 3208], 'An': [2966, 4056, 4912], 'non-ion-paired': [2974], 'Asp-76': [2978, 3006, 3077, 3144, 4204], 'T1': [2981, 3009, 4207, 4265], 'very': [3012], 'low': [3013, 3061, 3168, 3266, 3923], '0.6': [3016, 4211], 'forms': [3018, 4451, 4458, 4956], 'intramolecular': [3020, 4453], 'Asn-9,': [3028], 'Tyr-11,': [3029], 'Thr-91': [3031], 'see': [3052], 'responsible': [3058], 'pK,': [3062, 4472], 'removed': [3067], 'time,': [3071], 'measured.': [3078, 5477], 'single': [3080, 3529, 4573], 'removed,': [3084, 3096, 3109], 'increases': [3088, 3100, 3112, 4567, 4625], '3.3.': [3090], '5.1.': [3102], '6.4.': [3114, 3157], 'Thus,': [3115], 'absence': [3118], 'elevated': [3126], '2.5': [3127], 'increase': [3133, 3467, 3541, 3658, 4595, 5103, 5407], 'combine': [3170, 4486], '5.8': [3180], 'comprehensive': [3184], 'description': [3185], 'due': [3190, 5196], 'per': [3214, 4170, 4690, 4700, 4825], 'bond': [3216], '1.6': [3222], 'Major': [3231], 'forces': [3232, 3349, 4584, 5384], 'favoring': [3233, 3255], 'folding': [3234, 4011, 5283], 'globular': [3236, 3261, 4591, 4608], 'bonding,': [3244], 'able': [3249], 'overcome': [3251], 'major': [3253, 4583], 'force': [3254], 'unfolding,': [3256], 'conformational': [3257, 3267, 4605], 'entropy,': [3258], 'surprisingly': [3265], '2–10': [3271], '(26Pace': [3273], 'Prabhakaran': [3277], 'Philos.': [3281], 'Trans.': [3282], 'Lond.': [3285], 'B': [3286], '2004;': [3289], '359:': [3290], '1225-1234Crossref': [3291], '(273)': [3294], 'now': [3299, 3811, 5294], 'clear': [3300, 3745], 'under': [3306, 3761], 'physiological': [3307, 3762], 'conditions': [3308, 3763], '(27Radivojac': [3309, 3764], 'Iakoucheva': [3311, 3766], 'L.M.': [3312, 3767], 'Oldfield': [3313, 3768], 'C.J.': [3314, 3769], 'Obradovic': [3315, 3770, 3833], 'Uversky': [3317, 3772, 3831], 'V.N.': [3318, 3773, 3832, 3905, 3969], 'Dunker': [3319, 3774, 3835], 'A.K.': [3320, 3775, 3836], '1439-1456Abstract': [3325, 3780], '(577)': [3333, 3788], 'fold': [3337], 'required': [3341], 'function.': [3344], 'Because': [3345, 5290], 'minor': [3348], '1–3': [3352], 'become': [3355, 3744], 'important.': [3356, 5289], 'Interactions—Charged': [3358], 'arranged': [3364], 'among': [3369, 5370], 'favorable.': [3372], 'arrangement': [3375], 'others': [3384], 'sometimes': [3387], '(28Spassov': [3389, 4828], 'Karshikoff': [3391, 4830], 'Ladenstein': [3393, 4832], '1994;': [3397, 4836], '3:': [3398, 4837], '1556-1569Crossref': [3399, 4838], '(58)': [3402, 4841], 'do': [3417, 3478], '10': [3429], '(29Pace': [3431], 'Laurents': [3433], 'Thomson': [3435], 'J.A.': [3436, 3816], 'Biochemistry.': [3437, 3576, 3599, 3618, 4328, 4865, 4946, 5161], '29:': [3439, 4330, 4867, 4948], '2564-2572Crossref': [3440], '(350)': [3443], 'Despite': [3446, 4198], 'ways.': [3458], 'There': [3459], 'considerable': [3461], 'developing': [3464], 'methods': [3465], 'substitutions.': [3473], 'difficult': [3476], 'burying': [3480], 'adding': [3484, 5045], 'done': [3490], 'improving': [3492, 5041], '(30Schweiker': [3502, 3546, 3674], 'Zarrine-Afsar': [3504, 3548, 3676], 'Davidson': [3506, 3550, 3678], 'A.R.': [3507, 3551, 3679, 4883], 'Makhatadze': [3508, 3552, 3597, 3680], 'G.I.': [3509, 3553, 3598, 3681], '16:': [3513, 3557, 3685], '2694-2702Crossref': [3514, 3558, 3686], '(49)': [3517, 3561, 3689], 'Several': [3520], 'reversing': [3524], 'improve': [3537, 3697, 3861], '>1': [3544], '31Bi': [3564], 'Y.': [3565], 'Cho': [3566], 'Kim': [3568], 'E.Y.': [3569], 'Shan': [3570], 'Schindelin': [3572], 'Raleigh': [3574, 4020], 'D.P.': [3575, 4021], '46:': [3578], '7497-7505Crossref': [3579], '(29)': [3582], '32Strickler': [3585], 'S.S.': [3586], 'Gribenko': [3587], 'A.V.': [3588], 'Keiffer': [3589], 'T.R.': [3590], 'Tomlinson': [3591], 'Reihle': [3593], 'T.': [3594, 3818, 4648, 4751, 5154], 'Loladze': [3595], 'V.V.': [3596], '45:': [3601], '2761-2766Crossref': [3602], '(255)': [3605], '33Schwehm': [3608], 'Dang': [3612], 'B.N.': [3613], '42:': [3620], '1118-1128Crossref': [3621], '(38)': [3624], '34Grimsley': [3627], 'Fee': [3631], 'L.R.': [3632], 'Alston': [3633], 'R.W.': [3634], '1843-1849Crossref': [3647], '(197)': [3650], 'approach': [3654, 3694, 5403, 5568], 'guidelines': [3665], 'doing': [3669], '(Another': [3692], 'β-turns': [3699], '(35Trevino': [3706], 'S.R.': [3707, 4390, 4531, 5437, 5588], 'Schaefer': [3708], '373:': [3718], '211-218Crossref': [3719], '(112)': [3722], 'Just': [3725], 'attractive': [3727, 4816, 4846], 'stabilize': [3731, 4194], 'repulsive': [3734, 4808, 4822], 'destabilize': [3738, 4196], 'regions': [3753], 'polypeptide': [3756], 'disordered': [3760, 3804], 'IDPs,': [3797, 3802], '2The': [3798], 'abbreviation': [3799], 'is:': [3801], 'intrinsically': [3803], 'identified': [3809], '(36Sickmeier': [3813], 'Hamilton': [3815], 'LeGall': [3817], 'Vacic': [3819], 'V.': [3820], 'Cortese': [3821], 'Tantos': [3823], 'Szabo': [3825], 'Tompa': [3827], 'Chen': [3829], 'Nucleic': [3837], '35:': [3841], 'D786-D793Crossref': [3842], '(650)': [3845], 'revelation': [3849], 'surprising,': [3851], 'upon': [3853], 'reflection,': [3854], 'IDPs': [3855, 3919], 'offer': [3856], 'functions': [3858, 3864], 'known': [3863, 5124], '(37Dyson': [3867], 'H.J.': [3868], 'Wright': [3869], 'Nat.': [3871, 5062, 5109], 'Cell': [3874], '6:': [3877], '197-208Crossref': [3878], '(2999)': [3881], 'Two': [3884], 'hydrophobicity': [3900, 3963], '(38Uversky': [3904, 3968], 'Gillespie': [3906, 3970], 'J.R.': [3907, 3971], 'Fink': [3908, 3972], 'A.L.': [3909, 3973], '2000;': [3911, 3975, 4668, 4771, 5065, 5112], '41:': [3912, 3976], '415-427Crossref': [3913, 3977], '(1753)': [3916, 3980], 'hydrophobicity,': [3924], 'both.': [3930], 'border': [3932], 'well': [3941, 5349, 5392], 'following': [3944], 'equation:': [3945], '〈R〉': [3946, 3952], '2.785〈H〉': [3948], '1.151,': [3950], '〈H〉': [3954], 'mean': [3957, 3962], 'respectively': [3967], 'Recent': [3983, 5429], 'denatured': [3996], 'ensemble': [3998], 'mechanism': [4009, 4742], '(39Cho': [4012], 'Sato': [4014], 'Horng': [4016], 'Anil': [4018], 'Arch.': [4022], '469:': [4026], '20-28Crossref': [4027], '(39)': [4030], 'Ionizable': [4034], 'Residues—As': [4035], 'above,': [4037], 'improved': [4057], 'version': [4058], 'finite': [4061], 'Poisson-Boltzmann': [4063], 'method': [4064], 'estimate': [4068], '(40Kim': [4075, 4630, 4708], 'Mao': [4077, 4632, 4710], 'Gunner': [4079, 4634, 4712], '348:': [4085, 4640, 4718], '1283-1298Crossref': [4086, 4641, 4719], '(91)': [4089, 4644, 4722], 'dehydration': [4097], 'penalty': [4098], 'calculated.': [4100], 'great': [4104], 'enough': [4105], 'residue': [4116, 5419, 5578], 'classed': [4118], 'buried.': [4120, 4163], '>80%': [4126], 'accessible': [4131], 'area': [4133], 'Using': [4138], 'criterion,': [4140], '32%': [4141], '19%': [4146], '13%': [4151], '6%': [4157], 'amounts': [4165], '4': [4167], '100': [4171, 4691, 4701, 4826], 'composition': [4175], '41%': [4177], '28%': [4179], '22%': [4181], '9%': [4184], 'being': [4199], 'stability.': [4259, 4298], 'D76A': [4261], 'mutation': [4262], '3.8': [4267], 'less': [4269, 4426], 'stable': [4270, 4427, 4436, 5122, 5263], 'wild-type': [4273, 4439, 4521], 'suggests': [4278, 5249], '∼8': [4294], 'Asp-70': [4302, 4920, 4955, 4969], 'T4': [4304, 4924, 5012], 'lysozyme': [4305, 4925], '0.5,': [4312], '(41Anderson': [4322, 4859, 4940], 'D.E.': [4323, 4860, 4941], 'Becktel': [4324, 4861, 4942], 'W.J.': [4325, 4862, 4943], 'Dahlquist': [4326, 4863, 4944], 'F.W.': [4327, 4864, 4945], '2403-2408Crossref': [4331, 4868, 4949], '(478)': [4334, 4871, 4952], 'Asp-33,': [4347], '99%': [4350], '2.4,': [4357], 'Asp-79,': [4359], '85%': [4362], '7.4': [4369], '42Trevino': [4389], 'Gokulan': [4391, 4532], 'Mitkevich': [4399, 4540], 'V.A.': [4400, 4541], 'Makarov': [4401, 4542], 'A.A.': [4402, 4543], '354:': [4413, 4554], '967-978Crossref': [4414, 4555], '(28)': [4417, 4558], 'D33A': [4421], 'mutant': [4422, 4431, 4509], '6': [4424], 'D79A': [4430], '3.3': [4433], 'different:': [4449], 'Asp-33': [4450, 4466], 'Asp-79': [4457, 4476], 'none.': [4459], '+7': [4464], 'ionizes,': [4467, 4477], '–6': [4474], 'environmental': [4484], 'give': [4488], 'markedly': [4496], 'different': [4497, 5020], 'D79F': [4508], '3.7': [4516], 'enzyme,': [4522], 'raises': [4525], 'Tm': [4527, 5136], '(10': [4528], '°C)': [4529], '(42Trevino': [4530], 'largest': [4566], 'mutation.': [4574], 'we': [4578], 'size': [4598, 4629], 'increases.': [4599], 'observed:': [4603], 'independent': [4611], 'size.': [4613], 'shown': [4617], '43Kajander': [4647], 'Kahn': [4649, 4752], 'P.C.': [4650, 4753], 'Passila': [4651, 4754], 'S.H.': [4652, 4755], 'Cohen': [4653, 4756], 'D.C.': [4654, 4757], 'Lehtio': [4655, 4758], 'Adolfsen': [4657, 4760], 'W.': [4658, 4761], 'Warwicker': [4659, 4762], 'Goldman': [4663, 4766], 'Struct.': [4665, 4768, 5063, 5110], 'Folding': [4666, 4769], 'Des.': [4667, 4770], '1203-1214Abstract': [4670, 4773], '(99)': [4677, 4780], '1.9': [4689], '<100': [4696], '4.5': [4699], '>300': [4706], 'seems': [4726], 'likely': [4727], 'hydrogen-bonded': [4737], 'ion-paired': [4739], 'evolution': [4744], 'uses': [4745], '(43Kajander': [4750], 'Ion': [4783], 'Pairs—Attractive': [4784], 'nearby': [4787], '(<5Å)': [4788], 'oppositely': [4789], 'called': [4793], 'pairs': [4795, 4818, 4848, 5047, 5224, 5252], 'salt': [4797, 4917, 4930, 4958, 5003, 5081, 5097], 'bridges.': [4798], 'Coulombic': [4799], 'made': [4804], 'avoiding': [4807], 'interactions;': [4810], 'there': [4813], 'pair': [4824], 'Whether': [4844], 'favorably': [4850], 'controversial': [4856], 'topic,': [4857], 'experimentally': [4858], '44Horovitz': [4874], 'Serrano': [4876], 'Avron': [4878], 'Bycroft': [4880], 'Fersht': [4882], '216:': [4888], '1031-1044Crossref': [4889], '(390)': [4892], 'theoretically': [4896], '(45Kumar': [4897], 'Nussinov': [4899], '293:': [4905], '1241-1255Crossref': [4906], '(372)': [4909], 'bridge': [4918, 4931, 4959, 5004], 'His-31': [4922, 4986], 'His-31,': [4961], 'perturbs': [4965], 'values:': [4968], '0.5': [4974], '3.5–4': [4980], 'whereas': [4985], '9.1': [4991], '6.8': [4997], 'contributes': [5005], '∼4': [5006], 'lysozyme.': [5013], 'Proteins': [5014], 'thermophiles': [5016], 'stabilized': [5018], 'ways': [5021], '(46Petsko': [5022, 5048], 'G.A.': [5023, 5049], 'Methods': [5024, 5050], 'Enzymol.': [5025, 5051], '2001;': [5026, 5052], '334:': [5027, 5053], '469-478Crossref': [5028, 5054], '(126)': [5031, 5057], 'strategy': [5036], '47Pace': [5060], '7:': [5066, 5113], '345-346Crossref': [5067, 5114], '(74)': [5070, 5117], 'Thermophilic': [5073], 'bridges': [5082, 5098], 'mesophiles,': [5086], 'lines': [5089], 'suggest': [5092, 5564], 'temperatures': [5106], '(47Pace': [5107], 'CutA1': [5127, 5184, 5211], 'hyperthermophile': [5131], 'Pyrococcus': [5132], 'horikoshii,': [5133], '∼150': [5138], '°C': [5139], '7': [5142], '(48Sawano': [5143], 'Yamamoto': [5145], 'Ogasahara': [5147], 'Kidokoro': [5149], 'Katoh': [5151, 5155], 'Ohnuma': [5153], 'Yokoyama': [5157], 'Yutani': [5159], '47:': [5163], '721-730Crossref': [5164], '(27)': [5167], 'bacteria,': [5175], 'plants,': [5176], 'animals,': [5178], 'including': [5179], 'humans.': [5180], 'All': [5181], 'studied': [5186], 'remarkably': [5188], 'stable,': [5189], 'thought': [5193], 'part': [5198], 'trimeric': [5202], 'structure.': [5203], 'striking': [5206], 'horikoshii': [5210], 'same': [5214], 'Escherichia': [5217], 'coli': [5218], 'monomer:': [5227], '30': [5228], 'hyperthermophile,': [5236], 'mesophile.': [5247], 'crucial': [5255], 'importance': [5256], 'solubility': [5266, 5298, 5310, 5357, 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