Deep Shashank, Ahluwalia J C
Department of Chemistry, Indian Institute of Technology, Hauz Khas, New Delhi 110016, India.
Protein Eng. 2003 Jun;16(6):415-22. doi: 10.1093/protein/gzg050.
Atomic solvation parameters (ASPs) are widely used to estimate the solvation contribution to the thermodynamic stability of proteins as well as the free energy of association for protein-ligand complexes. In view of discrepancies in the results of free energies of solvation of folding for various proteins obtained using different atomic solvation parameter sets, systematic studies have been carried out for the calculation of accessible surface area and the changes in free energy of solvation of folding (deltaG(s,f)) for mutants of lysozyme T4 where threonine 157 is replaced by amino acids: cysteine, aspartate, glutamate, phenylalanine, glycine, histidine, isoleucine, leucine, asparagine, arginine, serine and valine. The deviations of the calculated results from the experimental results are discussed to highlight the discrepancies in the atomic solvation parameter sets and possible reasons for them. The results are also discussed to throw light on the effect of chain free energy and hydrogen bonding on the stability of mutants. The octanol to water-based ASP sets 'Sch1' and 'EM' perform better than the vacuum to water-based ASP sets. The vacuum to water-based ASP sets 'Sch3' and 'WE' can be used to predict the stability of mutants if a proper method to calculate the hydrogen bond contribution to overall stability is in place.
原子溶剂化参数（ASPs）被广泛用于估算溶剂化对蛋白质热力学稳定性的贡献以及蛋白质 - 配体复合物的结合自由能。鉴于使用不同原子溶剂化参数集获得的各种蛋白质折叠溶剂化自由能结果存在差异，已对溶菌酶T4的突变体进行了系统研究，其中苏氨酸157被以下氨基酸取代：半胱氨酸、天冬氨酸、谷氨酸、苯丙氨酸、甘氨酸、组氨酸、异亮氨酸、亮氨酸、天冬酰胺、精氨酸、丝氨酸和缬氨酸，以计算可及表面积和折叠溶剂化自由能的变化（deltaG(s,f)）。讨论了计算结果与实验结果的偏差，以突出原子溶剂化参数集的差异及其可能原因。还讨论了结果以阐明链自由能和氢键对突变体稳定性的影响。基于正辛醇 - 水的ASP集“Sch1”和“EM”比基于真空 - 水的ASP集表现更好。如果有适当的方法来计算氢键对整体稳定性的贡献，则基于真空 - 水的ASP集“Sch3”和“WE”可用于预测突变体的稳定性。
