Molecular Dynamics Study of Naturally Existing Cavity Couplings in Proteins

被引:8
作者
Barbany, Montserrat [1 ]
Meyer, Tim [2 ]
Hospital, Adam [3 ]
Faustino, Ignacio [3 ]
D'Abramo, Marco [4 ]
Morata, Jordi [5 ]
Orozco, Modesto [3 ,6 ]
de la Cruz, Xavier [1 ,7 ]
机构
[1] Vall dHebron Res Inst VHIR, Translat Bioinformat Neurosci, Barcelona, Spain
[2] Max Planck Inst Biophys Chem, Theoret & Comp Gestutzte Biophys, D-37077 Gottingen, Germany
[3] BSC, Joint IRB Inst Res Biomed, Program Computat Biol, Barcelona, Spain
[4] Univ Roma La Sapienza, Dept Chem, I-00185 Rome, Italy
[5] CRAG, Barcelona, Spain
[6] Univ Barcelona, Fac Biol, Dept Bioquim & Biol Mol, Barcelona, Spain
[7] ICREA, Barcelona, Spain
来源
PLOS ONE | 2015年 / 10卷 / 03期
关键词
RETINOL-BINDING-PROTEIN; N-TERMINAL RESIDUES; CONFORMATIONAL STABILITY; HUMAN LYSOZYME; CRYSTAL-STRUCTURE; ALLOSTERIC REGULATION; LIGAND; RECOGNITION; SIMULATION; MOTIONS;
D O I
10.1371/journal.pone.0119978
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
Couplings between protein sub-structures are a common property of protein dynamics. Some of these couplings are especially interesting since they relate to function and its regulation. In this article we have studied the case of cavity couplings because cavities can host functional sites, allosteric sites, and are the locus of interactions with the cell milieu. We have divided this problem into two parts. In the first part, we have explored the presence of cavity couplings in the natural dynamics of 75 proteins, using 20 ns molecular dynamics simulations. For each of these proteins, we have obtained two trajectories around their native state. After applying a stringent filtering procedure, we found significant cavity correlations in 60% of the proteins. We analyze and discuss the structure origins of these correlations, including neighbourhood, cavity distance, etc. In the second part of our study, we have used longer simulations (>= 100ns) from the MoDEL project, to obtain a broader view of cavity couplings, particularly about their dependence on time. Using moving window computations we explored the fluctuations of cavity couplings along time, finding that these couplings could fluctuate substantially during the trajectory, reaching in several cases correlations above 0.25/0.5. In summary, we describe the structural origin and the variations with time of cavity couplings. We complete our work with a brief discussion of the biological implications of these results.
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页数:28
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