Protein-peptide interactions play essential functional roles in living organisms and their structural characterization is a hot subject of current experimental theoretical research. Computational modeling the structure protein-peptide usually divided into two stages: prediction binding site at protein receptor surface, then docking (and modeling) peptide known site. This paper presents comprehensive CABS-dock method for simultaneous search sites flexible docking, available as users friendly...

We discuss the use of velocity rescaling for generating rejection-free exchange moves in replica molecular dynamics. test efficiency this approach a common case, trp-cage protein. Advantages and limitations are discussed possible extensions outlined.

This paper explores how and why FVFLM peptides can be used as model systems to inhibit beta-amyloid aggregation.

We analyze the dependence of cooperativity thermal denaturation transition and folding rates globular proteins on number amino acid residues, $N$, using lattice models with side chains,off-lattice Go available experimental data. A dimensionless measure cooperativity, $\Omega_c$ ($0 < \Omega_c \infty$), scales as $\Omega_c \sim N^{\zeta}$. The results simulations analysis data further confirm earlier prediction that $\zeta$ is universal $\zeta = 1 +\gamma$, where exponent $\gamma$...

Despite much progress in understanding the aggregation process of biomolecules, factors that govern its rates have not been fully understood. This problem is particular importance since many conformational diseases such as Alzheimer, Parkinson, and type-II diabetes are associated with protein oligomerization. Having performed all-atom simulations explicit water various force fields for two short peptides KFFE NNQQ, we show their oligomer formation times strongly correlated population...

Atomic-level molecular dynamics simulations are widely used for the characterization of structural proteins; however, they limited to shorter time scales than duration most relevant biological processes. Properly designed coarse-grained models that trade atomic resolution efficient sampling allow access much longer time-scales. In-depth understanding dynamics, must involve details. In this study, we tested a method rapid reconstruction all-atom from α carbon atom positions in application...

Fibril formation resulting from protein misfolding and aggregation is a hallmark of several neurodegenerative diseases such as Alzheimer's Parkinson's diseases. Despite much progress in the understanding process, factors governing fibril rates stability have not been fully understood. Using lattice models, we shown that time controlled by kinetic state but its energy. Having performed all-atom explicit solvent molecular dynamics simulations with GROMOS43a1 force field for full-length amyloid...

We have developed a new extended replica exchange method to study thermodynamics of system in the presence external force. Our idea is based on between different force replicas accelerate equilibrium process. This approach was applied obtain force-temperature phase diagram and other thermodynamical quantities three-domain ubiquitin. Using Cα-Go model Langevin dynamics, we shown that refolding pathways single ubiquitin depend which terminus fixed. If N end fixed then folding are compared case...

Mechanical unfolding of the fourth domain Distyostelium discoideum filamin (DDFLN4) was studied in detail using C$_{\alpha}$-Go model. We show that pathways this protein depend on pulling speed. The agreement between theoretical and experimental results sequencing events is achieved at low loading rates. free energy landscape also constructed dependencies forces speeds.

We study wild type and mutants of the A B domain protein G using all-atom Go-models. Our data substantiate usefulness such simulation for probing folding mechanism proteins demonstrate that multifunnel versions models also allow more complicated funnel landscapes. In our case, reproduce experimentally observed distributions GA98 GB98 which differ only by one residue but fold into different structures. They reveal details on in these two proteins.

Protein-peptide interactions play essential roles in many cellular processes and their structural characterization is the major focus of current experimental theoretical research. Two decades ago, it was proposed to employ steered molecular dynamics (SMD) assess strength protein-peptide interactions. The idea behind using SMD simulations that mechanical stability can be used as a promising an efficient alternative computationally highly demanding estimation binding affinity. However, defined...

Fibril formation resulting from protein misfolding and aggregation is a hallmark of several neurodegenerative diseases such as Alzheimer’s Parkinson’s diseases. Despite the fact that fibril process very slow thus poses significant challenge for theoretical experimental studies, number alternative pictures molecular mechanisms amyloid have been recently proposed. What seems to be common majority proposed models elongation involves pre-nucleus seeds prior creation critical nucleus. Once size...

We describe a combination of all-atom simulations with CABS, well-established coarse-grained protein modeling tool, into single multiscale protocol. The simulation method has been tested on the C-terminal beta hairpin G, model system folding. After reconstructing atomistic details, conformations derived from CABS were subjected to replica-exchange molecular dynamics OPLS-AA and AMBER99sb force fields in explicit solvent. Such accelerates convergence several times comparison starting extended...

Mechanical unfolding of the fourth domain Distyostelium discoideum filamin (DDFLN4) was studied by all-atom molecular dynamics simulations, using GROMOS96 force field 43a1 and simple point charge explicit water solvent. Our study reveals an important role non-native interactions in process. Namely, existence a peak centered at end-to-end extension DeltaR approximately 22 nm force-extension curve is associated with breaking hydrogen bonds. Such has been observed experiments but not Go models,...

Fluctuations of protein three-dimensional structures and large-scale conformational transitions are crucial for the biological function proteins their complexes. Experimental studies such phenomena remain very challenging therefore molecular modeling can be a good alternative or valuable supporting tool investigation large systems long-time events. In this mini-review, we present two approaches to coarse-grained (CG) dynamic properties systems. We discuss CG representations polypeptide...

We discuss the use of a structure based Cα-Go model and Langevin dynamics to study in detail mechanical properties unfolding pathway titin I27 domain. show that simple Go-model does detect correctly origin stability this The free energy landscape parameters xu ΔG‡, extracted from dependencies forces on pulling speeds, are found agree reasonably well with experiments. predict above v = 104 nm/s additional force-induced intermediate state is populated at an end-to-end extension about 75 Å....

The impact of the quenched force on protein folding pathways and free energy landscape was studied in detail. Using coarse-grain Go model, we have obtained low, middle, high regimes for refolding under force. low regime coincide with thermal ones. A clear switch from to force-driven middle observed. distance between denatured state transition xf temperature-driven is smaller than one. consistent available experimental data suggesting that atomic microscopy experiments deal force-regime which...