Balancing multiple objectives in conformation sampling to control decoy diversity in template-free protein structure prediction.

Balancing multiple objectives in conformation sampling to control decoy diversity in template-free protein structure prediction.

Zaman, Ahmed Bin;Shehu, Amarda;
BMC Bioinformatics 2019 Vol. 20 pp. 211
260
zaman2019balancingbmc

Abstract

Computational approaches for the determination of biologically-active/native three-dimensional structures of proteins with novel sequences have to handle several challenges. The (conformation) space of possible three-dimensional spatial arrangements of the chain of amino acids that constitute a protein molecule is vast and high-dimensional. Exploration of the conformation spaces is performed in a sampling-based manner and is biased by the internal energy that sums atomic interactions. Even state-of-the-art energy functions that quantify such interactions are inherently inaccurate and associate with protein conformation spaces overly rugged energy surfaces riddled with artifact local minima. The response to these challenges in template-free protein structure prediction is to generate large numbers of low-energy conformations (also referred to as decoys) as a way of increasing the likelihood of having a diverse decoy dataset that covers a sufficient number of local minima possibly housing near-native conformations.In this paper we pursue a complementary approach and propose to directly control the diversity of generated decoys. Inspired by hard optimization problems in high-dimensional and non-linear variable spaces, we propose that conformation sampling for decoy generation is more naturally framed as a multi-objective optimization problem. We demonstrate that mechanisms inherent to evolutionary search techniques facilitate such framing and allow balancing multiple objectives in protein conformation sampling. We showcase here an operationalization of this idea via a novel evolutionary algorithm that has high exploration capability and is also able to access lower-energy regions of the energy landscape of a given protein with similar or better proximity to the known native structure than several state-of-the-art decoy generation algorithms.The presented results constitute a promising research direction in improving decoy generation for template-free protein structure prediction with regards to balancing of multiple conflicting objectives under an optimization framework. Future work will consider additional optimization objectives and variants of improvement and selection operators to apportion a fixed computational budget. Of particular interest are directions of research that attenuate dependence on protein energy models.

Citation

ID: 22053
Ref Key: zaman2019balancingbmc
Use this key to autocite in SciMatic or Thesis Manager

References

Blockchain Verification

Account:
NFT Contract Address:
0x95644003c57E6F55A65596E3D9Eac6813e3566dA
Article ID:
22053
Unique Identifier:
10.1186/s12859-019-2794-5
Network:
Scimatic Chain (ID: 481)
Loading...
Blockchain Readiness Checklist
Authors
Abstract
Journal Name
Year
Title
5/5
Creates 1,000,000 NFT tokens for this article
Token Features:
  • ERC-1155 Standard NFT
  • 1 Million Supply per Article
  • Transferable via MetaMask
  • Permanent Blockchain Record
Blockchain QR Code
Scan with Saymatik Web3.0 Wallet

Saymatik Web3.0 Wallet