Topological properties of the configurational space of proteins (original) (raw)
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Searching Peptide Conformational Space
Journal of Chemical Theory and Computation, 2011
We have performed a near complete analysis of the conformational space in terms of minima and transition structures for four small peptide models with a force field energy function. There is a clear trend that minima having a large difference in structure, as measured by the distance in torsional space, are rarely connected by a single transition structure. There is a similar trend that activation energies for conformational transitions correlate with structure differences, such that small conformational changes occur with low energy barriers and vice versa. This suggests that a systematic search for low energy conformational transition structures should focus on pairs of minima that are structurally similar. Eigenvectors from diagonalization of force constant matrices at minima are better at describing conformational transitions than vibrational normal modes, as verified both by overlaps with geometry difference vectors and results from biased molecular dynamics simulations.
A topological approach for analyzing the protein structure
Persistent homology is a new tool from algebraic topology, showing until nowadays a lot of success when it comes to application in biology since this latest use metrics only for measuring similarities, Embedding the geometric details and focusing on the global shape is the key point making the success of persistent homology as an efficient topological data analysis tool. In this work we will be confirming the latest assumption (topology embeds geometry) by analyzing the structure of COILED SERINE which is a protein estimated to constitute 3-5 percent of the encoded residues in most genomes, and giving a substitute of the optimal characteristic distance that can be used in the flexibility-rigidity index, a classic method used to simulate molecule movements and flexible behavior, when it comes to atomic rigidity functions. We will also analyze interesting patterns in the binding site of the beta sheet generated from the pdb file 2JOX. We will be detecting and giving a simple descripti...
A Topological Data Analysis of the Protein Structure
A Topological Data Analysis of the Protein Structure, 2023
Persistent homology is a tool from a set of methods called Topological data analysis, showing until nowadays a lot of success when it comes to application in biology since this latest uses metrics only for measuring similarities, Embedding the geometric details and focusing on the global shape is the key point making the success of persistent homology, this will be investigated in the paper since enormous work already done in the field and results seems to be endless, as an efficient topological data analysis tool. In this work we will be confirming the latest assumption (topology embeds geometry) by displaying the structure of COILED SERINE which is a protein estimated to constitute 3-5 percent of the encoded residues in most genomes, and giving a substitute of the optimal characteristic distance that can be used in the flexibility-rigidity index, a classic method used to simulate molecule movements and flexible behavior, when it comes to atomic rigidity functions. We will also analyze interesting patterns in the binding site of the beta sheet generated from the pdb file 2JOX. We will be detecting and giving a simple description of different patterns generated by using javaplex generating barcodes and linear statistical results as a summary statistics.
Proteins: Structure, Function, and Genetics, 1995
Using energy minimization and cluster analysis, we have analyzed a 1020 ps molecular dynamics trajectory of solvated bovine pancreatic trypsin inhibitor. Elucidation of conformational substates in this way both illustrates the degree of conformational convergence in the simulation and reduces the structural data to a tractable subset. The relative movement of structures upon energy minimization was used to estimate the sizes of features on the protein potential energy surface. The structures were analyzed using their pairwise root-mean-square C, deviations, which gave a global measure of conformational changes that would not be apparent by monitoring single degrees of freedom. At time scales of 0.1 ps, energy minimization detected sharp transitions between energy minima separated by 0.1 A rms deviation. Larger conformational clusters containing these smaller minima and separated by 0.25 A were seen at 1 ps time scales. Both of these small features of the conformational landscape were characterized by movements in loop regions associated with small, correlated backbone dihedral angle shifts. On a nanosecond time scale, the main features of the protein energy landscape were clusters separated by over 0.7 A rms deviation, with only seven of these substates visited over the 1 ns trajectory. These substates, discernible both before and after energy minimization, differ mainly in a monotonic pivot of the loop residues 11-18 over the course of the simulation. This loop contains lysine 17, which specifically binds to trypsin in the active site. The trajectory did not return to previously visited clusters, indicating that this trajectory has not been shown to have completely sampled the conformational substates available to it. Because the apparent convergence to a single region of conformation space depends on both the time scale of observation and the size of the conformational features examined, convergence must be operationally defined within the context of the simulation. 0 1995 Wiley-Liss, Inc. C 1995 WILEY-LISS. INC.
Topological aspects of the conformational transformations in polypeptides and proteins
Biopolymers, 1983
The topological aspects of the conformational transformations in proteins are investigated using a new peptide-ribbon representation of the tertiary structure. The topological parameters evaluated on a set of 49 proteins show striking regularities that extend beyond the secondary structures actually present and are interpreted as a manifestation of the topological invariance of conformational transformations in globular proteins.
Evolution of physics-based methodology for exploring the conformational energy landscape of proteins
Journal of Computational Chemistry, 2002
The evolution of our physics-based computational methods for determining protein conformation without the introduction of secondary-structure predictions, homology modeling, threading, or fragment coupling is described. Initial use of a hard-sphere potential captured much of the structural properties of polypeptide chains, and subsequent more refined force fields, together with efficient methods of global optimization provide indications that progress is being made toward an understanding of the interresidue interactions that underlie protein folding.
Computational Study of the Conformational Domains of Peptide T
Journal of Peptide Science, 1997
The conformational preferences of peptide T (ASTTTNYT) were analysed by means of computational methods. A thorough exploration of the conformational space was carried out within the framework of the molecular mechanics approach, using simulated annealing as a searching strategy. Specifically, in order to obtain a subset of low-energy conformations with energies close to the global minimum as complete as possible, a simulated annealing protocol was repeated several times in a recursive fashion. The results of the search indicate that the peptide exhibits a a-helical character although most of the conformations characterized, including the global minimum, can be described as bent conformations. Conformations exhibiting b-turn motives previously proposed from NMR studies were also characterized, although they are not very predominant in the set of low-energy conformations.
Exploring the Stability of Dimers Through Protein Structure Topology
Protein homodimers pose some intriguing questions about the relation between structure and stability. We approached the problem by means of a topological methodology based on protein contact networks. We correlated local interface descriptors with structure and energy global properties of the systems under analysis. We demonstrated that the graph energy, formerly applied to the analysis of unconjugated hydrocarbons structures, is the bridge between the topological and energetic description of protein complexes. This is a first step for the generation of a " protein structural formula " , analogous to the molecular graphs in organic chemistry.
Protein folding and the organization of the protein topology universe
Trends in Biochemical Sciences, 2005
The mechanism by which proteins fold to their native states has been the focus of intense research in recent years. The rate-limiting event in the folding reaction is the formation of a conformation in a set known as the transition-state ensemble. The structural features present within such ensembles have now been analysed for a series of proteins using data from a combination of biochemical and biophysical experiments together with computer-simulation methods. These studies show that the topology of the transition state is determined by a set of interactions involving a small number of key residues and, in addition, that the topology of the transition state is closer to that of the native state than to that of any other fold in the protein universe. Here, we review the evidence for these conclusions and suggest a molecular mechanism that rationalizes these findings by presenting a view of protein folds that is based on the topological features of the polypeptide backbone, rather than the conventional view that depends on the arrangement of different types of secondary-structure elements. By linking the folding process to the organization of the protein structure universe, we propose an explanation for the overwhelming importance of topology in the transition states for protein folding.