@article {416, title = {Selection of optimal variants of Go-like models of proteins through studies of stretching.}, journal = {Biophys J}, volume = {95}, year = {2008}, month = {2008 Oct}, pages = {3174-91}, abstract = {The Go-like models of proteins are constructed based on the knowledge of the native conformation. However, there are many possible choices of a Hamiltonian for which the ground state coincides with the native state. Here, we propose to use experimental data on protein stretching to determine what choices are most adequate physically. This criterion is motivated by the fact that stretching processes usually start with the native structure, in the vicinity of which the Go-like models should work the best. Our selection procedure is applied to 62 different versions of the Go model and is based on 28 proteins. We consider different potentials, contact maps, local stiffness energies, and energy scales--uniform and nonuniform. In the latter case, the strength of the nonuniformity was governed either by specificity or by properties related to positioning of the side groups. Among them is the simplest variant: uniform couplings with no i, i + 2 contacts. This choice also leads to good folding properties in most cases. We elucidate relationship between the local stiffness described by a potential which involves local chirality and the one which involves dihedral and bond angles. The latter stiffness improves folding but there is little difference between them when it comes to stretching.}, keywords = {Analysis of Variance, Biomechanical Phenomena, Models, Molecular, Protein Conformation, Protein Folding, Proteins, Reproducibility of Results, Temperature, Thermodynamics}, issn = {1542-0086}, doi = {10.1529/biophysj.107.127233}, author = {Joanna I. Sulkowska and Cieplak, Marek} } @article {417, title = {Tightening of knots in proteins.}, journal = {Phys Rev Lett}, volume = {100}, year = {2008}, month = {2008 Feb 8}, pages = {058106}, abstract = {We perform theoretical studies of stretching of 20 proteins with knots within a coarse-grained model. The knot{\textquoteright}s ends are found to jump to well defined sequential locations that are associated with sharp turns, whereas in homopolymers they diffuse around and eventually slide off. The waiting times of the jumps are increasingly stochastic as the temperature is raised. Knots typically do not return to their native locations when a protein is released after stretching.}, keywords = {Algorithms, Diffusion, Models, Molecular, Protein Conformation, Solvents, Stochastic Processes, Temperature}, issn = {0031-9007}, author = {Joanna I. Sulkowska and Su{\l}kowski, Piotr and Szymczak, P and Cieplak, Marek} } @article {Kmiecik2007a, title = {Characterization of protein-folding pathways by reduced-space modeling}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {104}, number = {30}, year = {2007}, month = {jul}, pages = {12330{\textendash}5}, abstract = {Ab initio simulations of the folding pathways are currently limited to very small proteins. For larger proteins, some approximations or simplifications in protein models need to be introduced. Protein folding and unfolding are among the basic processes in the cell and are very difficult to characterize in detail by experiment or simulation. Chymotrypsin inhibitor 2 (CI2) and barnase are probably the best characterized experimentally in this respect. For these model systems, initial folding stages were simulated by using CA-CB-side chain (CABS), a reduced-space protein-modeling tool. CABS employs knowledge-based potentials that proved to be very successful in protein structure prediction. With the use of isothermal Monte Carlo (MC) dynamics, initiation sites with a residual structure and weak tertiary interactions were identified. Such structures are essential for the initiation of the folding process through a sequential reduction of the protein conformational space, overcoming the Levinthal paradox in this manner. Furthermore, nucleation sites that initiate a tertiary interactions network were located. The MC simulations correspond perfectly to the results of experimental and theoretical research and bring insights into CI2 folding mechanism: unambiguous sequence of folding events was reported as well as cooperative substructures compatible with those obtained in recent molecular dynamics unfolding studies. The correspondence between the simulation and experiment shows that knowledge-based potentials are not only useful in protein structure predictions but are also capable of reproducing the folding pathways. Thus, the results of this work significantly extend the applicability range of reduced models in the theoretical study of proteins.}, keywords = {Amino Acid Sequence, coarse-grained modeling, Computational Biology, Computer Simulation, Hydrophobic and Hydrophilic Interactions, Models, Molecular, Molecular Dynamics Simulation, Monte Carlo Method, Protein Denaturation, protein dynamics, Protein Folding, Protein Structure, Proteins, Proteins: chemistry, Proteins: metabolism, Temperature, Tertiary}, issn = {0027-8424}, doi = {10.1073/pnas.0702265104}, url = {http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1941469\&tool=pmcentrez\&rendertype=abstract}, author = {Sebastian Kmiecik and Andrzej Koli{\'n}ski} } @article {Gront2007, title = {T-Pile{\textendash}a package for thermodynamic calculations for biomolecules}, journal = {Bioinformatics (Oxford, England)}, volume = {23}, number = {14}, year = {2007}, month = {jul}, pages = {1840{\textendash}1842}, abstract = {Molecular dynamics and Monte Carlo, usually conducted in canonical ensemble, deliver a plethora of biomolecular conformations. Proper analysis of the simulation data is a crucial part of biophysical and bioinformatics studies. Sequence alignment problem can be also formulated in terms of Boltzmann distribution. Therefore tools for efficient analysis of canonical ensemble data become extremely valuable. T-Pile package, presented here provides a user-friendly implementation of most important algorithms such as multihistogram analysis and reweighting technique. The package can be used in studies of virtually any system governed by Boltzmann distribution. AVAILABILITY: T-Pile can be downloaded from: http://biocomp.chem.uw.edu.pl/services/tpile. These pages provide a comprehensive tutorial and documentation with illustrative examples of applications. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.}, keywords = {Algorithms, Biophysics, Biophysics: methods, Computational Biology, Computational Biology: methods, Computers, Hot Temperature, Models, Molecular Conformation, Monte Carlo Method, Probability, Proteins, Proteins: chemistry, Software, Temperature, Theoretical, Thermodynamics}, issn = {1367-4811}, doi = {10.1093/bioinformatics/btm259}, url = {http://www.ncbi.nlm.nih.gov/pubmed/17510173}, author = {Dominik Gront and Andrzej Koli{\'n}ski} } @article {Rutkowska2007, title = {Why do proteins divide into domains? Insights from lattice model simulations}, journal = {Biomacromolecules}, volume = {8}, year = {2007}, month = {nov}, pages = {3519{\textendash}24}, abstract = {

It is known that larger globular proteins are built from domains, relatively independent structural units. A domain size seems to be limited, and a single domain consists of from few tens to a couple of hundred amino acids. Based on Monte Carlo simulations of a reduced protein model restricted to the face centered simple cubic lattice, with a minimal set of short-range and long-range interactions, we have shown that some model sequences upon the folding transition spontaneously divide into separate domains. The observed domain sizes closely correspond to the sizes of real protein domains. Short chains with a proper sequence pattern of the hydrophobic and polar residues undergo a two-state folding transition to the structurally ordered globular state, while similar longer sequences follow a multistate transition. Homopolymeric (uniformly hydrophobic) chains and random heteropolymers undergo a continuous collapse transition into a single globule, and the globular state is much less ordered. Thus, the factors responsible for the multidomain structure of proteins are sufficiently long polypeptide chain and characteristic, protein-like, sequence patterns. These findings provide some hints for the analysis of real sequences aimed at prediction of the domain structure of large proteins.

}, keywords = {Computer Simulation, Models, Molecular, Polymers, Polymers: chemistry, Protein Structure, Proteins, Proteins: chemistry, Temperature, Tertiary}, issn = {1525-7797}, doi = {10.1021/bm7007718}, url = {http://www.ncbi.nlm.nih.gov/pubmed/17929971}, author = {Aleksandra Rutkowska and Andrzej Koli{\'n}ski} } @article {Gront2005b, title = {Protein structure prediction by tempering spatial constraints}, journal = {Journal of Computer-Aided Molecular Design}, volume = {19}, number = {8}, year = {2005}, month = {aug}, pages = {603{\textendash}8}, abstract = {The probability to predict correctly a protein structure can be enhanced through introduction of spatial constraints - either from NMR experiments or from homologous structures. However, the additional constraints lead often to new local energy minima and worse sampling efficiency in simulations. In this work, we present a new parallel tempering variant that alleviates the energy barriers resulting from spatial constraints and therefore yields to an enhanced sampling in structure prediction simulations.}, keywords = {Algorithms, Computer Simulation, Monte Carlo Method, Protein Conformation, Temperature}, isbn = {1082200590160}, issn = {0920-654X}, doi = {10.1007/s10822-005-9016-0}, url = {http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1473033\&tool=pmcentrez\&rendertype=abstract}, author = {Dominik Gront and Andrzej Koli{\'n}ski and Ulrich H. E. Hansmann} } @article {421, title = {Thermal unfolding of proteins.}, journal = {J Chem Phys}, volume = {123}, year = {2005}, month = {2005 Nov 15}, pages = {194908}, abstract = {Thermal unfolding of proteins is compared to folding and mechanical stretching in a simple topology-based dynamical model. We define the unfolding time and demonstrate its low-temperature divergence. Below a characteristic temperature, contacts break at separate time scales and unfolding proceeds approximately in a way reverse to folding. Features in these scenarios agree with experiments and atomic simulations on titin.}, keywords = {Chemistry, Physical, Computer Simulation, Connectin, Kinetics, Models, Molecular, Molecular Conformation, Muscle Proteins, Protein Conformation, Protein Denaturation, Protein Folding, Protein Kinases, Protein Structure, Secondary, Proteins, Temperature, Time Factors}, issn = {0021-9606}, doi = {10.1063/1.2121668}, author = {Cieplak, Marek and Joanna I. Sulkowska} } @article {Vinals2002, title = {Numerical study of the entropy loss of dimerization and the folding thermodynamics of the GCN4 leucine zipper}, journal = {Biophysical Journal}, volume = {83}, number = {5}, year = {2002}, month = {nov}, pages = {2801{\textendash}2811}, abstract = {A lattice-based model of a protein and the Monte Carlo simulation method are used to calculate the entropy loss of dimerization of the GCN4 leucine zipper. In the representation used, a protein is a sequence of interaction centers arranged on a cubic lattice, with effective interaction potentials that are both of physical and statistical nature. The Monte Carlo simulation method is then used to sample the partition functions of both the monomer and dimer forms as a function of temperature. A method is described to estimate the entropy loss upon dimerization, a quantity that enters the free energy difference between monomer and dimer, and the corresponding dimerization reaction constant. As expected, but contrary to previous numerical studies, we find that the entropy loss of dimerization is a strong function of energy (or temperature), except in the limit of large energies in which the motion of the two dimer chains becomes largely uncorrelated. At the monomer-dimer transition temperature we find that the entropy loss of dimerization is approximately five times smaller than the value that would result from ideal gas statistics, a result that is qualitatively consistent with a recent experimental determination of the entropy loss of dimerization of a synthetic peptide that also forms a two-stranded alpha-helical coiled coil.}, keywords = {Biophysical Phenomena, Biophysics, Databases as Topic, Dimerization, DNA-Binding Proteins, DNA-Binding Proteins: chemistry, Entropy, Hot Temperature, Leucine Zippers, Models, Monte Carlo Method, Protein Folding, Protein Kinases, Protein Kinases: chemistry, Saccharomyces cerevisiae Proteins, Saccharomyces cerevisiae Proteins: chemistry, Temperature, Theoretical, Thermodynamics}, issn = {0006-3495}, doi = {10.1016/S0006-3495(02)75289-2}, url = {http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1302364\&tool=pmcentrez\&rendertype=abstract}, author = {Jorge Vi{\~n}als and Andrzej Koli{\'n}ski and Jeffrey Skolnick} } @article {Mohanty1999, title = {De novo simulations of the folding thermodynamics of the GCN4 leucine zipper}, journal = {Biophysical Journal}, volume = {77}, number = {1}, year = {1999}, month = {jul}, pages = {54{\textendash}69}, abstract = {Entropy Sampling Monte Carlo (ESMC) simulations were carried out to study the thermodynamics of the folding transition in the GCN4 leucine zipper (GCN4-lz) in the context of a reduced model. Using the calculated partition functions for the monomer and dimer, and taking into account the equilibrium between the monomer and dimer, the average helix content of the GCN4-lz was computed over a range of temperatures and chain concentrations. The predicted helix contents for the native and denatured states of GCN4-lz agree with the experimental values. Similar to experimental results, our helix content versus temperature curves show a small linear decline in helix content with an increase in temperature in the native region. This is followed by a sharp transition to the denatured state. van{\textquoteright}t Hoff analysis of the helix content versus temperature curves indicates that the folding transition can be described using a two-state model. This indicates that knowledge-based potentials can be used to describe the properties of the folded and unfolded states of proteins.}, keywords = {Computer Simulation, Dimerization, DNA-Binding Proteins, Fungal Proteins, Fungal Proteins: chemistry, Leucine Zippers, Monte Carlo Method, Protein Conformation, Protein Denaturation, Protein Folding, Protein Kinases, Protein Kinases: chemistry, Protein Structure, Saccharomyces cerevisiae Proteins, Secondary, Temperature, Thermodynamics}, isbn = {6197848821}, issn = {0006-3495}, doi = {10.1016/S0006-3495(99)76872-4}, url = {http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1300312\&tool=pmcentrez\&rendertype=abstract}, author = {Debasisa Mohanty and Andrzej Koli{\'n}ski and Jeffrey Skolnick} } @article {Kolinski1986a, title = {Monte Carlo simulations on an equilibrium globular protein folding model}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {83}, number = {19}, year = {1986}, month = {oct}, pages = {7267{\textendash}71}, abstract = {

Monte Carlo simulations were performed on a diamond lattice, globular protein model in which the trans conformational state is energetically favored over the gauche states (thereby perhaps favoring a beta-sheet secondary structure) and in which nonspecific nonbonded nearest-neighbor attractive interactions are allowed. If the attractive interactions are sufficiently weak that the molecule possesses a relatively high fraction of trans states in the denatured state, then on collapse, a beta-barrel tertiary structure, highly reminiscent of the "native" structure seen in beta-proteins, spontaneously forms. If, however, the attractive interactions are dominant, a coil-to-random globule collapse transition is observed. The roles of short-, medium-, and long-range interactions and topological constraints in determining the observed tertiary structure are addressed, and the implications and limitations of the simulations for the equilibrium folding process in renal globular proteins are explored.

}, keywords = {Models, Protein Conformation, Statistics as Topic, Structural, Structure-Activity Relationship, Temperature, Thermodynamics}, issn = {0027-8424}, url = {http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=386697\&tool=pmcentrez\&rendertype=abstract}, author = {Andrzej Koli{\'n}ski and Jeffrey Skolnick and Robert Yaris} }