6,概率搜索和能量引导用于蛋白质结构从头预测中的偏向诱导采样.docVIP

Probabilistic Search and Energy Guidance for Biased Decoy Sampling in Ab-initio Protein Structure Prediction 概率搜索和能量引导用于蛋白质结构从头预测中的偏向诱导采样 Kevin Molloy, Sameh Saleh, and Amarda Shehu, Member, IEEE Abstract—Adequate sampling of the conformational space is a central challenge in ab-initio protein structure prediction. In the absence of a template structure, a conformational search procedure guided by an energy function explores the conformational space, gathering an ensemble of low-energy decoy conformations. If the sampling is inadequate, the native structure may be missed altogether. Even if reproduced, a subsequent stage that selects a subset of decoys for further structural detail and energetic refinement may discard near-native decoys if they are high-energy or insufficiently represented in the ensemble. Sampling should produce a decoy ensemble that facilitates the subsequent selection of near-native decoys. In this paper, we investigate a robotics-inspired framework that allows directly measuring the role of energy in guiding sampling. Testing demonstrates that a soft energy bias steers sampling towards a diverse decoy ensemble less prone to exploiting energetic artifacts and thus more likely to facilitate retainment of near-native conformations by selection techniques. We employ two different energy functions, the Associative Memory Hamiltonian with Water (AMW) and Rosetta.Results show that enhanced sampling provides a rigorous testing of energy functions and exposes different deficiencies in them, thus promising to guide development of more accurate representations and energy functions. Index Terms—Protein structure prediction, probabilistic conformational search, near-native conformations, energy bias. 摘要：在蛋白质结构从头预测中，足够的构象空间采样是一个核心的挑战。构象搜索程序在没有结构模板的情况下，由一个能量函数来引导其搜索构象空间，找到一个低能量的诱导构象集合。如果采样不足，天然态的结构就有可能全部丢失。即使重现，在后续阶段选择诱导构象的子集来进一步的对结构细节和能量进行优化，也可能由于它们是高能量或者不足以代表整个构象集合而丢失近天然态的诱导构象。采样应该产生一个诱导集合来促使后续的近天然态的诱导构象的选择。在这篇文章中，我们研究一个机器人启发式的框架，这个框架可以用来直接测试能量在引导采样的过程中所