Equilibrium simulations of proteins using molecular fragment replacement and NMR chemical shifts

Abstract

Significance Chemical shifts are the most fundamental parameters measured in nuclear magnetic resonance spectroscopy. Since these parameters are exquisitely sensitive to the local atomic environment, they can provide detailed information about the three-dimensional structures of proteins. It has recently been shown that using such information directly as input in molecular simulations based on the molecular fragment replacement strategy can help the process of protein structure determination. Here, we show how to implement this strategy to determine not only the structures of proteins but also their thermal fluctuations, thereby broadening the scope of chemical shifts in structural biology.