Biomolecular Interfaces, Latest Book by Ariel Fernandez (Springer International Publishing) (original) (raw)
Related papers
Opportunities and Challenges at Chemical and Biological Interfaces
Journal of Chemical and Biological Interfaces, 2013
Nanoscale thin films and molecular layers are the most common physical forms investigated in interfacial science. They are of substantial interest to a wide range of interdisciplinary researchers due to their specific chemical and biological functionalities, their contrasting behaviors to bulk forms, and their wide-ranging physical properties that are derived from the interface. This review provides a background to material that will be published in the Journal of Chemical and Biological Interfaces, as well as the numerous other vehicles for disseminating research across this broad scientific landscape. Opportunities and challenges are highlighted in relation to the fields of physics, chemistry, biology, materials science and bionanotechnology; and includes both experimental and computational studies relating to self-assembly of molecules, proteins and biomaterials; molecular thin films, Langmuir and Langmuir-Blodgett monolayers; chemical and biological sensors; organic electronics and photonics; in vitro construction of minimal cellular structures with cytoplasmic and extracellular environments; and surface sensitive characterization techniques.
Characterization of Protein–Protein Interfaces
Protein Journal, 2007
We analyze the characteristics of protein-protein interfaces using the largest datasets available from the Protein Data Bank (PDB). We start with a comparison of interfaces with protein cores and noninterface surfaces. The results show that interfaces differ from protein cores and non-interface surfaces in residue composition, sequence entropy, and secondary structure. Since interfaces, protein cores, and non-interface surfaces have different solvent accessibilities, it is important to investigate whether the observed differences are due to the differences in solvent accessibility or differences in functionality. We separate out the effect of solvent accessibility by comparing interfaces with a set of residues having the same solvent accessibility as the interfaces. This strategy reveals residue distribution propensities that are not observable by comparing interfaces with protein cores and noninterface surfaces. Our conclusions are that there are larger numbers of hydrophobic residues, particularly aromatic residues, in interfaces, and the interactions apparently favored in interfaces include the opposite charge pairs and hydrophobic pairs. Surprisingly, Pro-Trp pairs are over represented in interfaces, presumably because of favorable geometries. The analysis is repeated using three datasets having different constraints on sequence similarity and structure quality. Consistent results are obtained across these datasets. We have also investigated separately the characteristics of heteromeric interfaces and homomeric interfaces.
Bioinformation, 2017
Several catalysis, cellular regulation, immune function, cell wall assembly, transport, signaling and inhibition occur through Protein-Protein Interactions (PPI). This is possible with the formation of specific yet stable protein-protein interfaces. Therefore, it is of interest to understand its molecular principles using structural data in relation to known function. Several interface features have been documented using known X-ray structures of protein complexes since 1975. This has improved our understanding of the interface using structural features such as interface area, binding energy, hydrophobicity, relative hydrophobicity, salt bridges and hydrogen bonds. The strength of binding between two proteins is dependent on interface size (number of residues at the interface) and thus its corresponding interface area. It is known that large interfaces have high binding energy (sum of (van der Waals) vdW, H-bonds, electrostatics). However, the selective role played by each of these energy components and more especially that of vdW is not explicitly known. Therefore, it is important to document their individual role in known protein-protein structural complexes. It is of interest to relate interface size with vdW, H-bonds and electrostatic interactions at the interfaces of protein structural complexes with known function using statistical and multiple linear regression analysis methods to identify the prominent force. We used the manually curated non-redundant dataset of 278 hetero-dimeric protein structural complexes grouped using known functions by Sowmya et al. (2015) to gain additional insight to this phenomenon using a robust inter-atomic non-covalent interaction analyzing tool PPCheck (Anshul and Sowdhamini, 2015). This dataset consists of obligatory (enzymes, regulator, biological assembly), immune and nonobligatory (enzyme and regulator inhibitors) complexes. Results show that the total binding energy is more for large interfaces. However, this is not true for its individual energy factors. Analysis shows that vdW energies contribute to about 75% ±11% on average among all complexes and it also increases with interface size (r 2 ranging from 0.67 to 0.89 with p<0.01) at 95% confidence limit irrespective of molecular function. Thus, vdW is both dominant and proportional at the interface independent of molecular function. Nevertheless, H bond energy contributes to 15% ± 6.5% on average in these complexes. It also moderately increases with interface size (r 2 ranging from 0.43 to 0.61 with p<0.01) only among obligatory and immune complexes. Moreover, there is about 11.3% ± 8.7% contribution by electrostatic energy. It increases with interface size specifically among non-obligatory regulator-inhibitors (r 2 = 0.44). It is implied that both H-bonds and electrostatics are neither dominant nor proportional at the interface. Nonetheless, their presence cannot be ignored in binding. Therefore, H-bonds and (or) electrostatic energy having specific role for improved stability in complexes is implied. Thus, vdW is common at the interface stabilized further with selective H-bonds and (or) electrostatic interactions at an atomic level in almost all complexes. Comparison of this observation with residue level analysis of the interface is compelling. The role by H-bonds (14.83% ± 6.5% and r 2 = 0.61 with p<0.01) among obligatory and electrostatic energy (8.8% ± 4.77% and r 2 = 0.63 with p <0.01) among non-obligatory complexes within interfaces (class A) having more non-polar residues than surface is influencing our inference. However, interfaces (class B) having less non-polar residues than surface show 1.5 fold more electrostatic energy on average. The interpretation of the interface using inter-atomic (vdW, H-bonds, electrostatic) interactions combined with inter-residue predominance (class A and class B) in relation to known function is the key to reveal its molecular principles with new challenges.
Computational analyses of the surface properties of protein–protein interfaces
Acta Crystallographica Section D Biological Crystallography, 2007
Several potential applications of structural biology depend on discovering how one macromolecule might recognize a partner. Experiment remains the best way to answer this question, but computational tools can contribute where this fails. In such cases, structures may be studied to identify patches of exposed residues that have properties common to interaction surfaces and the locations of these patches can serve as the basis for further modelling or for further experimentation. To date, interaction surfaces have been proposed on the basis of unusual physical properties, unusual propensities for particular amino-acid types or an unusually high level of sequence conservation. Using the CXXSurface toolkit, developed as a part of the CCP4MG program, a suite of tools to analyse the properties of surfaces and their interfaces in complexes has been prepared and applied. These tools have enabled the rapid analysis of known complexes to evaluate the distribution of (i) hydrophobicity, (ii) electrostatic complementarity and (iii) sequence conservation in authentic complexes, so as to assess the extent to which these properties may be useful indicators of probable biological function.
Insights from the structural analysis of protein heterodimer interfaces
Bioinformation, 2011
Protein heterodimer complexes are often involved in catalysis, regulation, assembly, immunity and inhibition. This involves the formation of stable interfaces between the interacting partners. Hence, it is of interest to describe heterodimer interfaces using known structural complexes. We use a non-redundant dataset of 192 heterodimer complex structures from the protein databank (PDB) to identify interface residues and describe their interfaces using amino-acids residue property preference. Analysis of the dataset shows that the heterodimer interfaces are often abundant in polar residues. The analysis also shows the presence of two classes of interfaces in heterodimer complexes. The first class of interfaces (class A) with more polar residues than core but less than surface is known. These interfaces are more hydrophobic than surfaces, where protein-protein binding is largely hydrophobic. The second class of interfaces (class B) with more polar residues than core and surface is shown. These interfaces are more polar than surfaces, where binding is mainly polar. Thus, these findings provide insights to the understanding of protein-protein interactions.
BIOW@RE: a package of applications for intra/intermolecular interaction studies
The RIO family [1] of atypical protein kinases are present in organism varying from archea to humans. RIO1 and RIO2 are required for proper ribosome processing in yeast, and for proper cell cycle progression. Deletion of either RIO1 or RIO2 is lethal. Although the biological substrates of RIO kinases are still not known, this family is an important member of the regulation network in a cell. Hence, we decided to search for potential candidates as inhibitors, using a modelling approach. Crystallographic structures of RIO1 [2] are the basis for this approach. They are, however, not sufficient. The starting point for modeling is, apart from modeling the missing loops, determination of the protonation states of the more than one hundred ionizable groups of the protein. Poisson-Boltzmann equations were solved (MEAD program package), using the OPLS force-field parameters in the GROMACS program. To determine the probabilities of protonation of different ionizable groups of the protein at different pH values, the DOPS package [3, 4] was used. Analysis of protonation states within different potential binding sites will be presented. References: 1. LaRonde-LeBlanc N, Wlodawer SA (2005) The RIO kinases: An atypical protein kinase family required for ribosome biogenesis and cell cycle progression. BBA 1754: 14-24. 2. LaRonde-LeBlanc N, Guszczynski T, Copeland T, Wlodawer A (2005) Structure and activity of the atypical serine kinase Rio FEBS J. 272: 3698-3713. 3. Antosiewicz J, Poerschke D (1989) The nature of protein dipole moments: Experiment and calculated protein dipole of αchymotripsin. Biochemistry 28: 10072-10078. 4. Antosiewicz J (1995) Computation of the dipole moment of protein. Biophysical
Small protein–protein interfaces rich in electrostatic are often linked to regulatory function
Journal of Biomolecular Structure and Dynamics, 2019
Protein-protein interaction (PPI) is critical for several biological functions in living cells through the formation of an interface. Therefore, it is of interest to characterize protein-protein interfaces using an updated non-redundant structural dataset of 2557 homo (identical subunits) and 393 hetero (different subunits) dimer protein complexes determined by X-ray crystallography. We analyzed the interfaces using van der Waals (vdW), hydrogen bonding and electrostatic energies. Results show that on average homo and hetero interfaces are similar. Hence, we further grouped the 2950 interfaces based on percentage vdW to total energies into dominant (60%) and subdominant (<60%) vdW interfaces. Majority (92%) of interfaces have dominant vdW energy with large interface size (146 ± 87 (homo) and 137 ± 76 (hetero) residues) and interface area (1622 ± 1135 Å 2 (homo) and 1579 ± 1060 Å 2 (hetero)). However, a proportion (8%) of interfaces have subdominant vdW energy with small interface size (85 ± 46 (homo) and 88 ± 36 (hetero) residues) and interface area (823 ± 538 Å 2 (homo) and 881 ± 377 Å 2 (hetero)). It is found that large interfaces have twofold more interface area and interface size than small interfaces with increasing hydrogen bonding energy to interface size. However, small interfaces have threefold more electrostatics energy than large interfaces with increasing electrostatics to interface size. Thus, 8% of complexes having small interfaces with limited interface area and subdominant vdW energy are rich in electrostatics. It is interesting to observe that complexes having small interfaces are often associated with regulatory function. Hence, the observed structural features with known molecular function provide insights for the better understanding of PPI.
Analysing six types of protein–protein interfaces
2003
Non-covalent residue side-chain interactions occur in many different types of proteins and facilitate many biological functions. Are these differences manifested in the sequence compositions and/or the residue-residue contact preferences of the interfaces? Previous studies analysed small data sets and gave contradictory answers. Here, we introduced a new data-mining method that yielded the largest high-resolution data set of interactions analysed. We introduced an information theory-based analysis method. On the basis of sequence features, we were able to differentiate six types of protein interfaces, each corresponding to a different functional or structural association between residues. Particularly, we found significant differences in amino acid composition and residue-residue preferences between interactions of residues within the same structural domain and between different domains, between permanent and transient interfaces, and between interactions associating homo-oligomers and hetero-oligomers. The differences between the six types were so substantial that, using amino acid composition alone, we could predict statistically to which of the six types of interfaces a pool of 1000 residues belongs at 63-100% accuracy. All interfaces differed significantly from the background of all residues in SWISS-PROT, from the group of surface residues, and from internal residues that were not involved in non-trivial interactions. Overall, our results suggest that the interface type could be predicted from sequence and that interface-type specific mean-field potentials may be adequate for certain applications.