@article {Trojanowski2010, title = {TRACER. A new approach to comparative modeling that combines threading with free-space conformational sampling}, journal = {Acta Biochimica Polonica}, volume = {57}, number = {1}, year = {2010}, month = {jan}, pages = {125{\textendash}33}, abstract = {A new approach to comparative modeling of proteins, TRACER, is described and benchmarked against classical modeling procedures. The new method unifies true three-dimensional threading with coarse-grained sampling of query protein conformational space. The initial sequence alignment of a query protein with a template is not required, although a template needs to be somehow identified. The template is used as a multi-featured fuzzy three-dimensional scaffold. The conformational search for the query protein is guided by intrinsic force field of the coarse-grained modeling engine CABS and by compatibility with the template scaffold. During Replica Exchange Monte Carlo simulations the model chain representing the query protein finds the best possible structural alignment with the template chain, that also optimizes the intra-protein interactions as approximated by the knowledge based force field of CABS. The benchmark done for a representative set of query/template pairs of various degrees of sequence similarity showed that the new method allows meaningful comparative modeling also for the region of marginal, or non-existing, sequence similarity. Thus, the new approach significantly extends the applicability of comparative modeling.}, keywords = {Computational Biology, Computational Biology: methods, Imaging, Models, Molecular, Protein Conformation, Proteins, Proteins: chemistry, Three-Dimensional, Three-Dimensional: methods}, issn = {1734-154X}, url = {http://www.ncbi.nlm.nih.gov/pubmed/20309433}, author = {Sebastian Trojanowski and Aleksandra Rutkowska 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 {Kmiecik2006, title = {Denatured proteins and early folding intermediates simulated in a reduced conformational space}, journal = {Acta Biochimica Polonica}, volume = {53}, number = {1}, year = {2006}, month = {jan}, pages = {131{\textendash}143}, abstract = {Conformations of globular proteins in the denatured state were studied using a high-resolution lattice model of proteins and Monte Carlo dynamics. The model assumes a united-atom and high-coordination lattice representation of the polypeptide conformational space. The force field of the model mimics the short-range protein-like conformational stiffness, hydrophobic interactions of the side chains and the main-chain hydrogen bonds. Two types of approximations for the short-range interactions were compared: simple statistical potentials and knowledge-based protein-specific potentials derived from the sequence-structure compatibility of short fragments of protein chains. Model proteins in the denatured state are relatively compact, although the majority of the sampled conformations are globally different from the native fold. At the same time short protein fragments are mostly native-like. Thus, the denatured state of the model proteins has several features of the molten globule state observed experimentally. Statistical potentials induce native-like conformational propensities in the denatured state, especially for the fragments located in the core of folded proteins. Knowledge-based protein-specific potentials increase only slightly the level of similarity to the native conformations, in spite of their qualitatively higher specificity in the native structures. For a few cases, where fairly accurate experimental data exist, the simulation results are in semiquantitative agreement with the physical picture revealed by the experiments. This shows that the model studied in this work could be used efficiently in computational studies of protein dynamics in the denatured state, and consequently for studies of protein folding pathways, i.e. not only for the modeling of folded structures, as it was shown in previous studies. The results of the present studies also provide a new insight into the explanation of the Levinthal{\textquoteright}s paradox.}, keywords = {Animals, Biophysics, Biophysics: methods, Chymotrypsin, Chymotrypsin: antagonists \& inhibitors, Chymotrypsin: chemistry, Computer Simulation, Cytochromes c, Cytochromes c: chemistry, Models, Molecular, Molecular Conformation, Monte Carlo Method, Protein Conformation, Protein Denaturation, Protein Folding, Ribonucleases, Ribonucleases: chemistry, src Homology Domains, Statistical}, issn = {0001-527X}, url = {http://www.ncbi.nlm.nih.gov/pubmed/16365636}, author = {Sebastian Kmiecik and Mateusz Kurcinski and Aleksandra Rutkowska and Dominik Gront and Andrzej Koli{\'n}ski} }