Leap‐dynamics: efficient sampling of conformational space of proteins and peptides in solution

FEBS Letters

Fraternali, Franca²  Kleinjung, Jens¹  Bayley, Peter¹ 

[1] Physical Biochemistry Division, National Institute for Medical Research, Mill Hill, London NW7 1AA, UK;Molecular Structure Division, National Institute for Medical Research, Mill Hill, London NW7 1AA, UK

关键词: Molecular dynamics;    Sampling;    Implicit solvent;    Protein motion;    BPTI;    bovine pancreatic trypsin inhibitor;    CED;    CONCOORD ‘essential dynamics’;    EM;    energy minimisation;    LD;    Leap-dynamics;    MD;    molecular dynamics;    NMR;    nuclear magnetic resonance;    rmsd;    root mean square deviation;   

DOI  :  10.1016/S0014-5793(00)01295-3

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

A molecular simulation scheme, called Leap-dynamics, that provides efficient sampling of protein conformational space in solution is presented. The scheme is a combined approach using a fast sampling method, imposing conformational ‘leaps’ to force the system over energy barriers, and molecular dynamics (MD) for refinement. The presence of solvent is approximated by a potential of mean force depending on the solvent accessible surface area. The method has been successfully applied to N-acetyl-L-alanine-N-methylamide (alanine dipeptide), sampling experimentally observed conformations inaccessible to MD alone under the chosen conditions. The method predicts correctly the increased partial flexibility of the mutant Y35G compared to native bovine pancreatic trypsin inhibitor. In particular, the improvement over MD consists of the detection of conformational flexibility that corresponds closely to slow motions identified by nuclear magnetic resonance techniques.

【 授权许可】

Unknown