Biology subjects

Rosenberg, A. A.

Publications and source records attributed to Rosenberg, A. A..

2 recordsLinked to original sources

bioRxiv2024

Seeing Double: Molecular dynamics simulations reveal the stability of certain alternate protein conformations in crystal structures

Proteins jiggle around, adopting ensembles of interchanging conformations. Here we show through a large-scale analysis of the Protein Data Bank and using molecular dynamics simulations, that segments of protein chains can also commonly adopt dual, transiently stable conformations which is not explained by direct interactions. Our analysis highlights how alternate conformations can be maintained as non-interchanging, separated states intrinsic to the protein chain, namely through steric barriers or the adoption of transient secondary structure elements. We further demonstrate that despite the commonality of the phenomenon, current structural ensemble prediction methods fail to capture these bimodal distributions of conformations.

biochemistry↗

bioRxiv2022

Defining amino acid pairs as structural units suggests mutation sensitivity toadjacent residues

Proteins fold from chains of amino acids, forming secondary structures, -helices and {beta}-strands, that, at least for globular proteins, subsequently fold into a three-dimensional structure. A large-scale analysis of high-resolution protein structures suggests that amino acid pairs constitute another layer of ordered structure, more local than these conventionally defined secondary structures. We develop a cross-peptide-bond Ramachandran plot that captures the conformational preferences of the amino acid pairs and show that the effect of a particular mutation on the stability of a protein depends in a predictable manner on the adjacent amino acid context. One-Sentence SummaryLarge-scale protein backbone analysis reveals amino acid pair conformational preferences and predicts how sequence context affects mutant stability.

molecular biology↗