Structure-Based Prediction of the Mobility and Disorder of Water Molecules at Protein-DNA Interface

Abstract

Water plays an invaluable role in governing the structure, stability, dynamics, and function of biomolecules, which has also been demonstrated to be critical in mediating biomolecular recognition and association. Accurate determination of the dynamic behavior of water molecules at biological complex interface is important for the understanding of the molecular mechanism of water contributing to the binding between biomolecules and could be exploited as an alternative tool to refine the water's positions in X-ray electron density map. In the present study, a method called local hydrophobic descriptors (LHDs) is used to characterize the hydrophobic landscapes of the hydration sites at protein-DNA interface. The resulting variables of the characterization are then correlated with the experimentally measured B-factor values of 4445 elaborately selected water samples derived from a panel of thematically nonredundant, high-quality protein-DNA interfaces by using a variety of machine learning methods, including PLS, BPNN, SVM, LSSVM, RF, and GP. The results show that the dynamic behavior of interfacial water molecules is primarily governed by the local hydrophobic feature of the hydration sites that water molecules located, and the nonlinear dependence dominates over the linear component in the water B-factor system. We expect that this structured-based approach can be used for predicting the B-factor profile of other biomolecules as well.

Protein flexibility in the light of structural alphabets

“…Indeed, water molecules mediate a proportionally largest number of contacts in the minor groove and form the largest proportion of contacts in complexes of transcription factors (Schneider et al, 2014 ). It corroborates to previous researches on the importance of mobility of such water molecules (Luo et al, 2011 ; Russo et al, 2011 ).…”

Annotating the protein-RNA interaction sites in proteins using evolutionary information and protein backbone structure

“…csie.nut.edu.tw/$ cjlin/libsvm) (Chang and Lin, 2011). The radial basis kernel is used (Cai et al, 2004;Chen et al, 2009Chen et al, , 2008Hu and Li, 2008;Huang et al, 2010a;Li et al, 2010a;Luo et al, 2011;Mohabatkar et al, 2011;Qiu et al, 2010;Shao et al, 2009;Shu et al, 2008;Zhou et al, 2007). Whole prediction procedure is illustrated in Fig.…”

Modeling of the Water Network at Protein–RNA Interfaces

“…Water plays an important role in biomolecular association. Water molecules at protein–protein and protein–oligonucleotide interfaces form extensive hydrogen-bonded networks and facilitate the formation and dissociation of these complexes. − Water molecules influence molecular recognition, specificity, and affinity of protein complexes with other proteins − and with DNA, − RNA, , and sugars . Water is also important in the interaction of proteins with small ligands, and recognition of the hydration status of a protein binding pocket may guide optimal drug design. , It is also apparent that not all water molecules at an interface are equivalent: some show rapid exchange with the bulk, while others are relatively tightly bound, and some water molecules bound to a protein surface prior to ligand binding are retained in complexes with small molecules and proteins .…”