Jump to main content
Jump to site search

Issue 1, 2017
Previous Article Next Article

Insights from molecular dynamics simulations for computational protein design

Author affiliations

Abstract

A grand challenge in the field of structural biology is to design and engineer proteins that exhibit targeted functions. Although much success on this front has been achieved, design success rates remain low, an ever-present reminder of our limited understanding of the relationship between amino acid sequences and the structures they adopt. In addition to experimental techniques and rational design strategies, computational methods have been employed to aid in the design and engineering of proteins. Molecular dynamics (MD) is one such method that simulates the motions of proteins according to classical dynamics. Here, we review how insights into protein dynamics derived from MD simulations have influenced the design of proteins. One of the greatest strengths of MD is its capacity to reveal information beyond what is available in the static structures deposited in the Protein Data Bank. In this regard simulations can be used to directly guide protein design by providing atomistic details of the dynamic molecular interactions contributing to protein stability and function. MD simulations can also be used as a virtual screening tool to rank, select, identify, and assess potential designs. MD is uniquely poised to inform protein design efforts where the application requires realistic models of protein dynamics and atomic level descriptions of the relationship between dynamics and function. Here, we review cases where MD simulations were used to modulate protein stability and protein function by providing information regarding the conformation(s), conformational transitions, interactions, and dynamics that govern stability and function. In addition, we discuss cases where conformations from protein folding/unfolding simulations have been exploited for protein design, yielding novel outcomes that could not be obtained from static structures.

Graphical abstract: Insights from molecular dynamics simulations for computational protein design

Back to tab navigation
Please wait while Download options loads

Publication details

The article was received on 21 Sep 2016, accepted on 03 Jan 2017, published on 09 Jan 2017 and first published online on 09 Jan 2017


Article type: Review Article
DOI: 10.1039/C6ME00083E
Citation: Mol. Syst. Des. Eng., 2017,2, 9-33
  •   Request permissions

    Insights from molecular dynamics simulations for computational protein design

    M. C. Childers and V. Daggett, Mol. Syst. Des. Eng., 2017, 2, 9
    DOI: 10.1039/C6ME00083E

Search articles by author