论文标题
PARCE：通过计算进化的氨基酸改进方案
PARCE: Protocol for Amino acid Refinement through Computational Evolution
论文作者
论文摘要
由于其低不良反应和主要特异性，肽和蛋白质作为粘合剂的硅硅设计在诊断和治疗剂中很有用。为了选择最有希望的候选人，关键是要了解他们与蛋白质靶标的相互作用。在这项工作中，我们提出了PARCE，这是一种通过计算进化来进行氨基酸改进的开源协议，该计算进化实现了一种高级且有前途的肽和蛋白质设计方法。该协议在粘合剂序列中执行随机突变，然后使用分子动力学模拟进行结合构象，并评估来自多个评分的蛋白质 - 蛋白质相互作用。最后，它通过根据结合分数应用共识标准来接受或拒绝突变。该程序的迭代旨在探索有效新颖的序列，并具有对目标的潜在更好的亲和力。我们还提供了运行和复制方法的教程。
The in silico design of peptides and proteins as binders is useful for diagnosis and therapeutics due to their low adverse effects and major specificity. To select the most promising candidates, a key matter is to understand their interactions with protein targets. In this work, we present PARCE, an open source Protocol for Amino acid Refinement through Computational Evolution that implements an advanced and promising method for the design of peptides and proteins. The protocol performs a random mutation in the binder sequence, then samples the bound conformations using molecular dynamics simulations, and evaluates the protein-protein interactions from multiple scoring. Finally, it accepts or rejects the mutation by applying a consensus criterion based on binding scores. The procedure is iterated with the aim to explore efficiently novel sequences with potential better affinities toward their targets. We also provide a tutorial for running and reproducing the methodology.
