@inbook {545, title = {Explicit-Solvent All-Atom Molecular Dynamics of Peptide Aggregation}, booktitle = {Computational Methods to Study the Structure and Dynamics of Biomolecules and Biomolecular Processes: From Bioinformatics to Molecular Quantum Mechanics}, year = {2019}, pages = {541{\textendash}558}, publisher = {Springer International Publishing}, organization = {Springer International Publishing}, abstract = {Recent advances in computational technology have allowed us to simulate biomolecular processes on timescales that begin to reach the rates of peptide aggregation phenomena. Molecular dynamics simulations have evolved into a mature technique to the extent that they can be employed as a highly productive tool to gain meaningful insights into the structure, dynamics and molecular mechanisms of protein aggregation. In this chapter, we describe the basics of explicit solvent all-atom molecular dynamics simulations and its applications for studying early stages of aggregation processes of two short pentapeptides: KLVFF and FVFLM, related to Alzheimer{\textquoteright}s disease and preeclampsia, respectively. We focus on certain important problems in the field of protein aggregation that explicit solvent all-atom molecular dynamics simulation studies could resolve. This includes how fibril formation rates depend on a number of factors such as the presence of short peptides and population of fibril-prone conformations. Specific applications of atomistic simulations in explicit solvent to address these two issues are discussed.}, isbn = {978-3-319-95843-9}, doi = {10.1007/978-3-319-95843-9_16}, url = {https://doi.org/10.1007/978-3-319-95843-9_16}, author = {Maksim Kouza and Andrzej Koli{\'n}ski and Irina Buhimschi and Andrzej Kloczkowski} } @article {531, title = {Role of Resultant Dipole Moment in Mechanical Dissociation of Biological Complexes}, journal = {Molecules}, volume = {23(8)}, year = {2018}, month = {08/2018}, pages = {1995}, publisher = {MDPI}, abstract = {Protein-peptide interactions play essential roles in many cellular processes and their structural characterization is the major focus of current experimental and theoretical research. Two decades ago, it was proposed to employ the steered molecular dynamics (SMD) to assess the strength of protein-peptide interactions. The idea behind using SMD simulations is that the mechanical stability can be used as a promising and an efficient alternative to computationally highly demanding estimation of binding affinity. However, mechanical stability defined as a peak in force-extension profile depends on the choice of the pulling direction. Here we propose an uncommon choice of the pulling direction along resultant dipole moment (RDM) vector, which has not been explored in SMD simulations so far. Using explicit solvent all-atom MD simulations, we apply SMD technique to probe mechanical resistance of ligand-receptor system pulled along two different vectors. A novel pulling direction{\textemdash}when ligand unbinds along the RDM vector{\textemdash}results in stronger forces compared to commonly used ligand unbinding along center of masses vector. Our observation that RDM is one of the factors influencing the mechanical stability of protein-peptide complex can be used to improve the ranking of binding affinities by using mechanical stability as an effective scoring function.}, doi = {10.3390/molecules23081995}, url = {http://www.mdpi.com/1420-3049/23/8/1995}, author = {Maksim Kouza and Anirban Banerji and Andrzej Koli{\'n}ski and Irina Buhimschi and Andrzej Kloczkowski} }