Abstract
BackgroundBiological molecules are often asymmetric with respect to stereochemistry, and correct stereochemistry is essential to their function. Molecular dynamics simulations of biomolecules have increasingly become an integral part of biophysical research. However, stereochemical errors in biomolecular structures can have a dramatic impact on the results of simulations.ResultsHere we illustrate the effects that chirality and peptide bond configuration flips may have on the secondary structure of proteins throughout a simulation. We also analyze the most common sources of stereochemical errors in biomolecular structures and present software tools to identify, correct, and prevent stereochemical errors in molecular dynamics simulations of biomolecules.ConclusionsUse of the tools presented here should become a standard step in the preparation of biomolecular simulations and in the generation of predicted structural models for proteins and nucleic acids.
Highlights
Biological molecules are often asymmetric with respect to stereochemistry, and correct stereochemistry is essential to their function
Consequences of stereochemical errors in biomolecular simulations In order to understand more directly the effects that errors in chirality or peptide bond configuration have on secondary structure, consider three simulations involving a 15-amino-acid-long a-helix AAQAAAAQAAAAQAA solvated in water
The configuration of a peptide bond is central to the types of secondary structure the peptide chain can assume: only the trans isomer accepts and donates hydrogen bonds in opposite directions allowing for formation of a-helices and b-sheets
Summary
Biological molecules are often asymmetric with respect to stereochemistry, and correct stereochemistry is essential to their function. Molecular dynamics simulations of biomolecules have increasingly become an integral part of biophysical research. Many biologically active molecules are chiral, i.e., they exist in two forms, called enantiomers, which are non-superimposable mirror images of each other. All amino acids save glycine have at least one chiral center at Ca (see Figure 1A). Threonine and isoleucine have an additional chiral center at Cb. Interestingly, only one of the two enantiomers is widely used in nature: according to the D-/L-naming convention, most naturally occurring amino acids are found in the L-configuration. In DNA the atoms C1’, C3’, and C4’ of the sugar moiety are chiral, while in RNA the presence of an additional OH group renders C2’ of the ribose chiral (see Figure 1B). Due to the partial double-bond character of the Cn-Nn+1 bond, the atoms Ca, n, Cn, On, Ca, n+1, Nn+1 and its hydrogen are in a plane (see, Ref [9]) and the rotation around the Cn-Nn+1 bond
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