Spiwok Vojtěch, Oborský Pavel, Pazúriková Jana, Křenek Aleš, Králová Blanka
Department of Biochemistry and Microbiology, University of Chemistry and Technology, Prague, Technická 3, Prague 6 166 28, Czech Republic.
Institute of Computer Science, Masaryk University, Botanická 554/68a, 602 00 Brno, Czech Republic.
J Chem Phys. 2015 Mar 21;142(11):115101. doi: 10.1063/1.4914828.
Biased simulations have great potential for the study of slow processes, including protein folding. Atomic motions in molecules are nonlinear, which suggests that simulations with enhanced sampling of collective motions traced by nonlinear dimensionality reduction methods may perform better than linear ones. In this study, we compare an unbiased folding simulation of the Trp-cage miniprotein with metadynamics simulations using both linear (principle component analysis) and nonlinear (Isomap) low dimensional embeddings as collective variables. Folding of the mini-protein was successfully simulated in 200 ns simulation with linear biasing and non-linear motion biasing. The folded state was correctly predicted as the free energy minimum in both simulations. We found that the advantage of linear motion biasing is that it can sample a larger conformational space, whereas the advantage of nonlinear motion biasing lies in slightly better resolution of the resulting free energy surface. In terms of sampling efficiency, both methods are comparable.
有偏模拟在包括蛋白质折叠在内的缓慢过程研究中具有巨大潜力。分子中的原子运动是非线性的，这表明使用非线性降维方法增强集体运动采样的模拟可能比线性模拟表现更好。在本研究中，我们将色氨酸笼状小蛋白的无偏折叠模拟与使用线性（主成分分析）和非线性（等距映射）低维嵌入作为集体变量的元动力学模拟进行了比较。通过线性偏置和非线性运动偏置，在200纳秒的模拟中成功模拟了小蛋白的折叠。在两种模拟中，折叠态均被正确预测为自由能最小值。我们发现线性运动偏置的优势在于它可以采样更大的构象空间，而非线性运动偏置的优势在于所得自由能表面的分辨率略高。在采样效率方面，两种方法相当。
