A sequence space search engine for computational protein design to modulate molecular functionality

De-novo protein design explores the untapped sequence space that is otherwise less discovered during the evolutionary process. This necessitates an efficient sequence space search engine for effective convergence in computational protein design. We propose a greedy simulated annealing-based Monte-Ca...

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Veröffentlicht in:Journal of biomolecular structure & dynamics Jg. 41; H. 7; S. 2937 - 2946
Hauptverfasser: Malik, Ayush, Banerjee, Anupam, Pal, Abantika, Mitra, Pralay
Format: Journal Article
Sprache:Englisch
Veröffentlicht: England Taylor & Francis 03.05.2023
Schlagworte:
altering molecular functionality
Amino Acid Sequence
Computer Simulation
high native sequence recapitulation
Monte-Carlo parallel search algorithm
Protein design
protein sequence-structure compatibility
Proteins - chemistry
Search Engine
Solvents
Monte-Carlo parallel search algorithm
protein sequence-structure compatibility
high native sequence recapitulation
Protein design
altering molecular functionality
ISSN:0739-1102, 1538-0254, 1538-0254
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Zusammenfassung:De-novo protein design explores the untapped sequence space that is otherwise less discovered during the evolutionary process. This necessitates an efficient sequence space search engine for effective convergence in computational protein design. We propose a greedy simulated annealing-based Monte-Carlo parallel search algorithm for better sequence-structure compatibility probing in protein design. The guidance provided by the evolutionary profile, the greedy approach, and the cooling schedule adopted in the Monte Carlo simulation ensures sufficient exploration and exploitation of the search space leading to faster convergence. On evaluating the proposed algorithm, we find that a dataset of 76 target scaffolds report an average root-mean-square-deviation (RMSD) of 1.07 Å and an average TM-Score of 0.93 with the modeled designed protein sequences. High sequence recapitulation of 48.7% (59.4%) observed in the design sequences for all (hydrophobic) solvent-inaccessible residues again establish the goodness of the proposed algorithm. A high (93.4%) intra-group recapitulation of hydrophobic residues in the solvent-inaccessible region indicates that the proposed protein design algorithm preserves the core residues in the protein and provides alternative residue combinations in the solvent-accessible regions of the target protein. Furthermore, a COFACTOR-based protein functional analysis shows that the design sequences exhibit altered molecular functionality and introduce new molecular functions compared to the target scaffolds. Communicated by Ramaswamy H. Sarma
Bibliographie:ObjectType-Article-1
SourceType-Scholarly Journals-1
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content type line 23
ISSN:0739-1102
1538-0254
1538-0254
DOI:10.1080/07391102.2022.2042386