Papoian Garegin A, Ulander Johan, Eastwood Michael P, Luthey-Schulten Zaida, Wolynes Peter G
Department of Chemistry and Biochemistry and Center for Theoretical Biological Physics, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0371, USA.
Proc Natl Acad Sci U S A. 2004 Mar 9;101(10):3352-7. doi: 10.1073/pnas.0307851100. Epub 2004 Feb 26.
Proteins have evolved to use water to help guide folding. A physically motivated, nonpairwise-additive model of water-mediated interactions added to a protein structure prediction Hamiltonian yields marked improvement in the quality of structure prediction for larger proteins. Free energy profile analysis suggests that long-range water-mediated potentials guide folding and smooth the underlying folding funnel. Analyzing simulation trajectories gives direct evidence that water-mediated interactions facilitate native-like packing of supersecondary structural elements. Long-range pairing of hydrophilic groups is an integral part of protein architecture. Specific water-mediated interactions are a universal feature of biomolecular recognition landscapes in both folding and binding.
蛋白质已经进化到利用水来辅助引导折叠。将一种基于物理原理的、非成对加和的水介导相互作用模型添加到蛋白质结构预测哈密顿量中,可显著提高较大蛋白质结构预测的质量。自由能分布分析表明,长程水介导势引导折叠并使潜在的折叠漏斗变得平滑。对模拟轨迹的分析提供了直接证据,证明水介导的相互作用促进了超二级结构元件的类天然堆积。亲水性基团的长程配对是蛋白质结构的一个组成部分。特定的水介导相互作用是折叠和结合过程中生物分子识别格局的一个普遍特征。