Adhesive-cohesive model for protein compressibility: An alternative perspective on stability

被引:39
作者
Dadarlat, VM
Post, CB
机构
[1] Purdue Univ, Dept Chem, W Lafayette, IN 47907 USA
[2] Purdue Univ, Dept Med Chem, W Lafayette, IN 47907 USA
关键词
protein stability; enthalpy of protein unfolding; protein molecular dynamics; buried charge; unfolding heat capacity;
D O I
10.1073/pnas.2434157100
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
As a dynamic property of folded proteins, protein compressibility provides important information about the forces that govern structural stability. We relate intrinsic compressibility to stability by using molecular dynamics to identify a molecular basis for the variation in compressibility among globular proteins. We find that excess surface charge accounts for this variation not only for the proteins simulated by molecular dynamics but also for a larger set of globular proteins. This dependence on charge distribution forms the basis for an adhesive-cohesive model of protein compressibility in which attractive forces from solvent compete with tertiary interactions that favor folding. Further, a newly recognized correlation between compressibility and the heat capacity of unfolding infers a link between compressibility and the enthalpy of unfolding. This linkage, together with the adhesive-cohesive model for compressibility, leads to the conclusion that folded proteins can gain enthalpic stability from a uniform distribution of charged atoms, as opposed to partitioning charge to the protein surface. Whether buried charged groups can be energetically stabilizing is a fundamental, yet controversial, question regarding protein structure. The analysis reported here implies that one mechanism to gain enthalpic stability involves positioning charge inside the protein in an optimal structural arrangement.
引用
收藏
页码:14778 / 14783
页数:6
相关论文
共 41 条
[11]  
HENDSCH ZS, 1994, PROTEIN SCI, V3, P211
[12]  
Hill T. L., 1960, INTRO STAT THERMODYN
[13]   Protein folding: From the Levinthal paradox to structure prediction [J].
Honig, B .
JOURNAL OF MOLECULAR BIOLOGY, 1999, 293 (02) :283-293
[14]   Buried charged surface in proteins [J].
Kajander, T ;
Kahn, PC ;
Passila, SH ;
Cohen, DC ;
Lehtiö, L ;
Adolfsen, W ;
Warwicker, J ;
Schell, U ;
Goldman, A .
STRUCTURE, 2000, 8 (11) :1203-1214
[15]   HYDRATIONAL AND INTRINSIC COMPRESSIBILITIES OF GLOBULAR-PROTEINS [J].
KHARAKOZ, DP ;
SARVAZYAN, AP .
BIOPOLYMERS, 1993, 33 (01) :11-26
[16]   Salt bridge stability in monomeric proteins [J].
Kumar, S ;
Nussinov, R .
JOURNAL OF MOLECULAR BIOLOGY, 1999, 293 (05) :1241-1255
[17]  
Kurochkina N, 1998, PROTEIN SCI, V7, P897
[18]   Enthalpic contribution to protein stability: Insights from atom-based calculations and statistical mechanics [J].
Lazaridis, T ;
Archontis, G ;
Karplus, M .
ADVANCES IN PROTEIN CHEMISTRY, VOL 47, 1995, 47 :231-306
[19]   ISOENTHALPIC AND ISOENTROPIC TEMPERATURES AND THE THERMODYNAMICS OF PROTEIN DENATURATION [J].
LEE, B .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1991, 88 (12) :5154-5158
[20]   INTERPRETATION OF PROTEIN STRUCTURES - ESTIMATION OF STATIC ACCESSIBILITY [J].
LEE, B ;
RICHARDS, FM .
JOURNAL OF MOLECULAR BIOLOGY, 1971, 55 (03) :379-&