Sanches Murilo N, Parra R Gonzalo, Viegas Rafael G, Oliveira Antonio B, Wolynes Peter G, Ferreiro Diego U, Leite Vitor B P
Department of Physics, Institute of Biosciences, Humanities and Exact Sciences, São Paulo State University (UNESP), São José do Rio Preto, SP 15054-000, Brazil.
Barcelona Supercomputing Center (BSC), Barcelona, Spain.
QRB Discov. 2022 Jun 10;3:e7. doi: 10.1017/qrd.2022.4. eCollection 2022.
Ankyrin (ANK) repeat proteins are coded by tandem occurrences of patterns with around 33 amino acids. They often mediate protein-protein interactions in a diversity of biological systems. These proteins have an elongated non-globular shape and often display complex folding mechanisms. This work investigates the energy landscape of representative proteins of this class made up of 3, 4 and 6 ANK repeats using the energy-landscape visualisation method (ELViM). By combining biased and unbiased coarse-grained molecular dynamics AWSEM simulations that sample conformations along the folding trajectories with the ELViM structure-based phase space, one finds a three-dimensional representation of the globally funnelled energy surface. In this representation, it is possible to delineate distinct folding pathways. We show that ELViMs can project, in a natural way, the intricacies of the highly dimensional energy landscapes encoded by the highly symmetric ankyrin repeat proteins into useful low-dimensional representations. These projections can discriminate between multiplicities of specific parallel folding mechanisms that otherwise can be hidden in oversimplified depictions.
锚蛋白（ANK）重复蛋白由约33个氨基酸的模式串联出现编码。它们通常在多种生物系统中介导蛋白质 - 蛋白质相互作用。这些蛋白质具有细长的非球状形状，并且常常表现出复杂的折叠机制。这项工作使用能量景观可视化方法（ELViM）研究了由3个、4个和6个ANK重复组成的这类代表性蛋白质的能量景观。通过将有偏和无偏的粗粒度分子动力学AWSEM模拟（沿着折叠轨迹对构象进行采样）与基于ELViM结构的相空间相结合，人们找到了全局漏斗状能量表面的三维表示。在这种表示中，可以描绘出不同的折叠途径。我们表明，ELViM可以以自然的方式将由高度对称的锚蛋白重复蛋白编码的高维能量景观的复杂性投影到有用的低维表示中。这些投影可以区分特定平行折叠机制的多样性，否则这些多样性可能隐藏在过于简化的描述中。
