FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2268815883> ?p ?o ?g. }

• W2268815883 abstract "Spontaneous changes in protein systems, such as the binding of a ligand to an enzyme or receptor, are characterized by a decrease of free energy. Despite the recent developments in computing power and methodology, it remains challenging to accurately estimate free energy changes. Major issues are still concerned with the accuracy of the underlying model to describe the protein system and how well the calculation in fact emulates the behaviour of the system. This thesis is largely concerned with the quality of current free energy calculation methods as applied to protein-ligand systems. Several methodologies were employed to calculate Gibbs standard free energies of binding for a collection of protein-ligand complexes, for which experimental affinities were available. Calculations were performed using system description with different levels of accuracy and included a continuum approach, which considers the protein and the ligand at the atomic level but includes solvent as a polarizable continuum, and an all-atom approach that relies on molecular dynamics simulations. In most such applications, the effects of ionic strength are neglected. However, the severity of this approximation, in particular when calculating free energies of charged ligands, is not very clear. The issue of incorporating ionic strength in free energy calculations by means of explicit ions was investigated in greater detail and considerable attention was given to the affinities of charged peptides in the presence of explicit counter-ions. A second common approximation is concerned with the description of ligands that exhibit multiple protonation states. Because most of current methods do not model changes in the acid dissociation constants of titrating groups upon binding, protonation equilibria of such ligands are not taken into account in free energy calculations. The implications of this approximation when predicting affinities were analysed. Finally, when calculating free energies of binding, a correct description of the interactions between the protein and the ligand is of fundamental importance. However, active sites of enzymes, where strained conformations may hold a functional role, are not always accurately modelled by molecular mechanics force fields. The case of a strained planar proline in the active site of triosephosphate isomerase was investigated using an hybrid quantum mechanics/molecular mechanics method, which implies a higher level of accuracy." @default.
• W2268815883 created "2016-06-24" @default.
• W2268815883 creator A5049146628 @default.
• W2268815883 date "2007-01-01" @default.
• W2268815883 modified "2023-09-27" @default.
• W2268815883 title "Computing free energies of protein-ligand association" @default.
• W2268815883 cites W1491459594 @default.
• W2268815883 cites W1491642680 @default.
• W2268815883 cites W1491824558 @default.
• W2268815883 cites W1499452131 @default.
• W2268815883 cites W1504770578 @default.
• W2268815883 cites W1509876279 @default.
• W2268815883 cites W1515975222 @default.
• W2268815883 cites W1521042556 @default.
• W2268815883 cites W1527003521 @default.
• W2268815883 cites W157808733 @default.
• W2268815883 cites W1594487206 @default.
• W2268815883 cites W1596745037 @default.
• W2268815883 cites W1843397982 @default.
• W2268815883 cites W187801720 @default.
• W2268815883 cites W1889077695 @default.
• W2268815883 cites W1965378620 @default.
• W2268815883 cites W1967043736 @default.
• W2268815883 cites W1968344479 @default.
• W2268815883 cites W1968484323 @default.
• W2268815883 cites W1969512842 @default.
• W2268815883 cites W1970973025 @default.
• W2268815883 cites W1970991259 @default.
• W2268815883 cites W1972197313 @default.
• W2268815883 cites W1973657947 @default.
• W2268815883 cites W1974212746 @default.
• W2268815883 cites W1975755749 @default.
• W2268815883 cites W1980136543 @default.
• W2268815883 cites W1980381306 @default.
• W2268815883 cites W1980937780 @default.
• W2268815883 cites W1981021420 @default.
• W2268815883 cites W1981907708 @default.
• W2268815883 cites W1984738107 @default.
• W2268815883 cites W1985028250 @default.
• W2268815883 cites W1986240377 @default.
• W2268815883 cites W1988287340 @default.
• W2268815883 cites W1989557993 @default.
• W2268815883 cites W1989868941 @default.
• W2268815883 cites W1993177346 @default.
• W2268815883 cites W1995042715 @default.
• W2268815883 cites W1996451542 @default.
• W2268815883 cites W1999724806 @default.
• W2268815883 cites W2000268167 @default.
• W2268815883 cites W2003542620 @default.
• W2268815883 cites W2004303971 @default.
• W2268815883 cites W2010004274 @default.
• W2268815883 cites W2011447313 @default.
• W2268815883 cites W2013643300 @default.
• W2268815883 cites W2016111085 @default.
• W2268815883 cites W2016190213 @default.
• W2268815883 cites W2017019577 @default.
• W2268815883 cites W2017699465 @default.
• W2268815883 cites W2017829285 @default.
• W2268815883 cites W2017897721 @default.
• W2268815883 cites W2020276026 @default.
• W2268815883 cites W2022879191 @default.
• W2268815883 cites W2023592911 @default.
• W2268815883 cites W2024060531 @default.
• W2268815883 cites W2025391374 @default.
• W2268815883 cites W2026004905 @default.
• W2268815883 cites W2026499215 @default.
• W2268815883 cites W2027154929 @default.
• W2268815883 cites W2027978582 @default.
• W2268815883 cites W2029078760 @default.
• W2268815883 cites W2029087609 @default.
• W2268815883 cites W2031037667 @default.
• W2268815883 cites W2034399259 @default.
• W2268815883 cites W2035266068 @default.
• W2268815883 cites W2035432821 @default.
• W2268815883 cites W2037603210 @default.
• W2268815883 cites W2039545730 @default.
• W2268815883 cites W2041487385 @default.
• W2268815883 cites W2041902442 @default.
• W2268815883 cites W2043429268 @default.
• W2268815883 cites W2043543708 @default.
• W2268815883 cites W2045994733 @default.
• W2268815883 cites W2047631698 @default.
• W2268815883 cites W2048214699 @default.
• W2268815883 cites W2048389798 @default.
• W2268815883 cites W2052017179 @default.
• W2268815883 cites W2052656018 @default.
• W2268815883 cites W2054788798 @default.
• W2268815883 cites W2056760934 @default.
• W2268815883 cites W2061107874 @default.
• W2268815883 cites W2061545244 @default.
• W2268815883 cites W2066315281 @default.
• W2268815883 cites W2070648292 @default.
• W2268815883 cites W2071789190 @default.
• W2268815883 cites W2072162021 @default.
• W2268815883 cites W2073731045 @default.
• W2268815883 cites W2075901640 @default.
• W2268815883 cites W2077381233 @default.
• W2268815883 cites W2079199763 @default.
• W2268815883 cites W2080109130 @default.
• W2268815883 cites W2080634715 @default.

• next