Version 1
: Received: 7 September 2024 / Approved: 9 September 2024 / Online: 9 September 2024 (12:43:25 CEST)
How to cite:
Wang, C.; Mahmood, K.; Park, D. Evaluating Changes in the Local Protein Physicochemical Environment induced by Molecular Dynamics Simulation. Preprints2024, 2024090689. https://doi.org/10.20944/preprints202409.0689.v1
Wang, C.; Mahmood, K.; Park, D. Evaluating Changes in the Local Protein Physicochemical Environment induced by Molecular Dynamics Simulation. Preprints 2024, 2024090689. https://doi.org/10.20944/preprints202409.0689.v1
Wang, C.; Mahmood, K.; Park, D. Evaluating Changes in the Local Protein Physicochemical Environment induced by Molecular Dynamics Simulation. Preprints2024, 2024090689. https://doi.org/10.20944/preprints202409.0689.v1
APA Style
Wang, C., Mahmood, K., & Park, D. (2024). Evaluating Changes in the Local Protein Physicochemical Environment induced by Molecular Dynamics Simulation. Preprints. https://doi.org/10.20944/preprints202409.0689.v1
Chicago/Turabian Style
Wang, C., Khalid Mahmood and Daniel Park. 2024 "Evaluating Changes in the Local Protein Physicochemical Environment induced by Molecular Dynamics Simulation" Preprints. https://doi.org/10.20944/preprints202409.0689.v1
Abstract
Mutation of a single amino acid residue may significantly affect the structure and function of an entire protein. The effect of single amino acid substitutions can be assessed by examining the physicochemical environment surrounding the amino acid of interest, an emerging form of quantification of which is multidimensional tensors. However, the effect with respect to a protein variant’s inherent dynamics in tensor space is rarely assessed despite the potential importance of this form of analysis in revealing local physicochemical properties of the protein and response to mutation. Using the wild-type and 936 mutant structures of the protein domain 1pga, the present research evaluated the effects of local protein context and single amino acid substitutions on molecular dynamics simulation-derived structural distributions via the use of tensors capturing a range of biochemical properties. It was observed that the extent of simulated physicochemical variation local to a substituted amino acid is positively associated with local mechanical stiffness, loss of protein thermostability and decreased local hydrophobicity. In addition, it was observed that the largest tensor variation occurs in densely-packed, hydrophobic core-associated regions of protein structures. In summary, the pattern of tensor change aligns with prior knowledge about protein stability and physicochemical properties.
Keywords
molecular dynamics simulation; protein; single amino acid substitution; protein local physicochemical environment; tensors; variant effect prediction; FireProtDB
Subject
Biology and Life Sciences, Biochemistry and Molecular Biology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
