Solvent Accessibility Promotes Rotamer Errors during Protein Modeling with Major Side-Chain Prediction Programs.
J Chem Inf Model
; 63(14): 4405-4422, 2023 07 24.
Article
en En
| MEDLINE
| ID: mdl-37410883
ABSTRACT
Side-chain rotamer prediction is one of the most critical late stages in protein 3D structure building. Highly advanced and specialized algorithms (e.g., FASPR, RASP, SCWRL4, and SCWRL4v) optimize this process by use of rotamer libraries, combinatorial searches, and scoring functions. We seek to identify the sources of key rotamer errors as a basis for correcting and improving the accuracy of protein modeling going forward. In order to evaluate the aforementioned programs, we process 2496 high-quality single-chained all-atom filtered 30% homology protein 3D structures and use discretized rotamer analysis to compare original with calculated structures. Among 513,024 filtered residue records, increased amino acid residue-dependent rotamer errorsâassociated in particular with polar and charged amino acid residues (ARG, LYS, and GLN)âclearly correlate with increased amino acid residue solvent accessibility and an increased residue tendency toward the adoption of non-canonical off rotamers which modeling programs struggle to predict accurately. Understanding the impact of solvent accessibility now appears key to improved side-chain prediction accuracies.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Proteínas
/
Aminoácidos
Tipo de estudio:
Prognostic_studies
/
Risk_factors_studies
Idioma:
En
Revista:
J Chem Inf Model
Asunto de la revista:
INFORMATICA MEDICA
/
QUIMICA
Año:
2023
Tipo del documento:
Article
País de afiliación:
República Checa