Simplified Models for Simulating Replica Exchange Simulations and Recovering Kinetics of Protein Folding - read free eBook in online reader or directly download on the web page. Select files or add your book in reader. Download and read online ebook Simplified Models for Simulating Replica Exchange Simulations and Recovering Kinetics of Protein Folding write by Weihua Zheng. This book was released on 2009. Simplified Models for Simulating Replica Exchange Simulations and Recovering Kinetics of Protein Folding available in PDF, EPUB and Kindle. Protein folding is a fundamental problem in modern structural biology. The nature of the problem poses challenges to the understanding of the process via computer simulations. One of the challenges in the computer simulation of proteins at the atomic level is the efficiency of sampling conformational space. Replica exchange (RE) methods are widely employed to alleviate the difficulty. To study how to best employ RE to protein folding and binding problems, we constructed a kinetic network model for RE studies of protein folding and used this simplified model to carry out "simulations of simulations" to analyze how the underlying temperature dependence of the conformational kinetics and the basic parameters of RE all interact to affect the number of folding transitions observed. When protein folding follows anti-Arrhenius kinetics, we observe a speed limit for the number of folding transitions observed at the low temperature of interest, which depends on the maximum of the harmonic mean of the folding and unfolding transition rates at high temperature. The efficiency of temperature RE was also studied on a more complicated and realistic continuous two-dimensional potential. Comparison of the efficiencies obtained using the continuous and discrete models makes it possible to identify non-Markovian effects which slow down equilibration of the RE ensemble on the more complex continuous potential. In particular, the efficiency of RE is limited by the timescale of conformational relaxation within free energy basins. The other challenges we are facing in all-atom simulations is to obtain meaningful information on the slow kinetics and pathways of folding. We present a kinetic network model which recover the kinetics using RE-generated states as the nodes of a kinetic network. Choosing the appropriate neighbors and the microscopic rates between the neighbors, the correct kinetics of the system can be recovered by running a simulation on the network.
Replica-exchange Wang-landau Simulations of Lattice Proteins for the Understanding of the Protein Folding Problem
Replica-exchange Wang-landau Simulations of Lattice Proteins for the Understanding of the Protein Folding Problem - read free eBook in online reader or directly download on the web page. Select files or add your book in reader. Download and read online ebook Replica-exchange Wang-landau Simulations of Lattice Proteins for the Understanding of the Protein Folding Problem write by Guangjie Shi. This book was released on 2016. Replica-exchange Wang-landau Simulations of Lattice Proteins for the Understanding of the Protein Folding Problem available in PDF, EPUB and Kindle. Protein folding is studied within the context of two coarse-grained lattice models that separate all amino acids into only a few types. The hydrophobic-polar (HP) model is a simplified lattice protein model for simulating protein folding and for understanding many biological problems of interest. In this work, an "improved" model, the semi-flexible H0P model, was proposed by introducing a new type of "neutral" monomer, "0", i.e., neither hydrophobic nor polar and also taking into consideration the stiffness of bonds connecting monomers. Even though both models are highly simplified protein models, finding the lowest energy conformations and determining the density of states are extremely difficult. We applied replica-exchange Wang-Landau sampling with appropriate trial moves for determining the density of states of multiple HP and H0P proteins, from which the thermodynamic properties such as specific heat can be calculated. Moreover, we developed a heuristic method for determining the ground state degeneracy of lattice proteins, based on multicanonical sampling. It is applied during comprehensive studies of single-site mutations in specific lattice proteins with different sequences. The effects in which we are interested include structural changes in ground states, changes of ground state energy, degeneracy, and thermodynamic properties of the system. With respect to mutations, both extremely sensitive and insensitive positions in the protein sequence have been found. That is, ground state energies and degeneracies, as well as other thermodynamic and structural quantities may be either largely unaffected or may change significantly due to mutation. Moreover, comparison between the HP model and the semi-flexible H0P model have been performed based on two real proteins: Crambin and Ribonuclease A. We found that, compared with the HP model, the semi-flexible H0P model possesses significantly reduced ground state degeneracy, and rich folding signals as the proteins rearranging into native states from very compact structures at low temperatures. We calculated the free energy vs end-to-end distance as a function of temperature. The HP model shows a relatively shallow folding funnel and flat free energy minimum, reflecting the high degeneracy of the ground state. In contrast, the semi-flexible H0P model has a well developed, rough free energy funnel with a low degeneracy ground state. In both cases, folding funnels are asymmetric with temperature dependent shape.
Computer Simulations of Protein Folding and Aggregation
Computer Simulations of Protein Folding and Aggregation - read free eBook in online reader or directly download on the web page. Select files or add your book in reader. Download and read online ebook Computer Simulations of Protein Folding and Aggregation write by . This book was released on 2004. Computer Simulations of Protein Folding and Aggregation available in PDF, EPUB and Kindle. Computer simulation is used to study the competition between protein folding and aggregation, especially the formation of ordered structures that are also known as amyloid fibrils. Employing simplified protein models, we simulate multi-protein systems at a greater level of detail than has previously been possible, probe the fundamental physics that govern protein folding and aggregation, and explore the energetic and structural characteristics of amorphous and fibrillar protein aggregates. We first tackle the aggregation problem by using a low-resolution model called the lattice HP model developed by Lau and Dill. Dynamic Monte Carlo simulations are conducted on a system of simple, two-dimensional lattice protein molecules. We investigate how changing the rate of chemical or thermal renaturation affects the folding and aggregation behavior of the model protein molecule by simulating three renaturation methods: infinitely slow cooling, slow but finite cooling, and quenching. We find that the infinitely slow cooling method provides the highest refolding yields. We then study how the variation of protein concentration affects the refolding yield by simulating the pulse renaturation method, in which denatured proteins are slowly added to the refolding simulation box in a stepwise manner. We observe that the pulse renaturation method provides refolding yields that are substantially higher than those observed in the other three methods even at high packing fractions. We then investigate the folding of a polyalanine peptide with the sequence Ac-KA14K-NH2 using a novel off-lattice, intermediate-resolution protein model originally developed by Smith and Hall. The thermodynamics of a system containing a single Ac-KA14K-NH2 molecule is explored by employing the replica exchange simulation method to map out the conformational transitions as a function of temperature. We also explore the influence of solvent type on the folding process by varying the relative strength of the sid.
Markov Processes
Markov Processes - read free eBook in online reader or directly download on the web page. Select files or add your book in reader. Download and read online ebook Markov Processes write by Daniel T. Gillespie. This book was released on 1992. Markov Processes available in PDF, EPUB and Kindle. Markov process theory provides a mathematical framework for analyzing the elements of randomness that are involved in most real-world dynamical processes. This introductory text, which requires an understanding of ordinary calculus, develops the concepts and results of random variable theory.
Protein Folding Protocols
Protein Folding Protocols - read free eBook in online reader or directly download on the web page. Select files or add your book in reader. Download and read online ebook Protein Folding Protocols write by Yawen Bai. This book was released on 2008-02-04. Protein Folding Protocols available in PDF, EPUB and Kindle. Covering experiment and theory, bioinformatics approaches, and state-of-the-art simulation protocols for better sampling of the conformational space, this volume describes a broad range of techniques to study, predict, and analyze the protein folding process. Protein Folding Protocols also provides sample approaches toward the prediction of protein structure starting from the amino acid sequence, in the absence of overall homologous sequences.
