Identification and analysis of long‐range electrostatic effects in proteins by computer modeling:aspartate transcarbamylase

Oberoi, Himanshu; Trikha, J.; Yuan, Xin; Allewell, Norma M.

doi:10.1002/(sici)1097-0134(199607)25:3<300::aid-prot3>3.3.co;2-q

Cited by 18 publications

(17 citation statements)

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“…Thus, the observed asymmetry in the charge-backbone interactions follows directly from the nature of the peptide bond. Oberoi et al (1996) have noticed that most of the large chargebackbone interactions (1) are attractive, (2) are paired with a large positive Born term, and (3) correspond to anionic groups. Taking into consideration the asymmetry of charge-backbone interaction, discussed above, this observation can be generalized for the acidic groups in proteins.…”

Section: Asymmetry Of Charge-backbone Interactions In Proteinssupporting

confidence: 92%

“…It has been found that the ionizable groups are situated in regions where favorable interactions with the peptide dipoles occur (Olson & Spassov, 1987). This finding is consistent with the observation that the destabilizing effect of the charge dehydration is compensated by the electrostatic contribution of the peptide dipoles (Bashford & Karplus, 1990;Oberoi et al, 1996).…”

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confidence: 99%

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Optimization of the electrostatic interactions between ionized groups and peptide dipoles in proteins

1997

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The three-dimensional optimization of the electrostatic interactions between the charged amino acid residues and the peptide partial charges was studied by Monte-Carlo simulations on a set of 127 nonhomologous protein structures with known atomic coordinates. It was shown that this type of interaction is very well optimized for all proteins in the data set, which suggests that they are a valuable driving force, at least for the native side-chain conformations. Similar to the optimization of the charge-charge interactions (Spassov VZ, Karshikoff AD, Ladenstein R, 1995, Protein Sci 41516-1527), the optimization effect was found more pronounced for enzymes than for proteins without enzymatic function. The asymmetry in the interactions of acidic and basic groups with the peptide dipoles was analyzed and a hypothesis was proposed that the properties of peptide dipoles are a factor contributing to the natural selection of the basic amino acids in the chemical composition of proteins.

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Section: Asymmetry Of Charge-backbone Interactions In Proteinssupporting

confidence: 92%

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confidence: 99%

Optimization of the electrostatic interactions between ionized groups and peptide dipoles in proteins

1997

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“…The indirect interaction between the two members of this hydrogen bond would favor complex formation, since solvent would screen their favorable electrostatic interaction less in the bound state than in the unbound state. An important result of the work reported here is that energetics due to indirect effects are significant, though the importance of this term has generally not been recognized~Elcock & McCammon, 1996;Oberoi et al, 1996;Chong et al, 1998;Kangas & Tidor, 1998!. Summing each type of term for every group in the GCN4 leucine zipper~in a manner that counts each interaction once! showed that the electrostatic effect of complex formation is destabilizing because the unfavorable solvation term~24.0 kcal0mol!…”

Section: Resultsmentioning

confidence: 99%

Electrostatic interactions in the GCN4 leucine zipper: Substantial contributions arise from intramolecular interactions enhanced on binding

1999

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The GCN4 leucine zipper is a peptide homodimer that has been the subject of a number of experimental and theoretical investigations into the determinants of affinity and specificity. Here, we utilize this model system to investigate electrostatic effects in protein binding using continuum calculations. A particularly novel feature of the computations made here is that they provide an interaction-by-interaction breakdown of the electrostatic contributions to the free energy of docking that includes changes in the interaction of each functional group with solvent and changes in interactions between all pairs of functional groups on binding. The results show that~1! electrostatic effects disfavor binding by roughly 15 kcal0mol due to desolvation effects that are incompletely compensated in the bound state,~2! while no groups strongly stabilize binding, the groups that are most destabilizing are charged and polar side chains at the interface that have been implicated in determining binding specificity, and~3! attractive intramolecular interactions e.g., backbone hydrogen bonds! that are enhanced on binding due to reduced solvent screening in the bound state contribute significantly to affinity and are likely to be a general effect in other complexes. A comparison is made between the results obtained in an electrostatic analysis carried out calculationally and simulated results corresponding to idealized data from a scanning mutagenesis experiment. It is shown that scanning experiments provide incomplete information on interactions and, if overinterpreted, tend to overestimate the energetic effect of individual side chains that make attractive interactions. Finally, a comparison is made between the results available from a continuum electrostatic model and from a simpler surface-area dependent solvation model. In this case, although the simpler model neglects certain interactions, on average it performs rather well.

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“…Electrostatic interactions depend on the attraction and repulsion of charged groups and the consequent desolvation of these groups 114. Charge interactions are important because they can influence protein stability and ligand binding, which in turn affect the structure and solvation of molecules 115–117. Polyanions form electrostatic interactions primarily with lysine and arginine residues within proteins.…”

Section: Specific Versus Non‐specific Interactionsmentioning

confidence: 99%

The role of RNA in mammalian prion protein conversion

et al. 2011

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Prion diseases remain a challenge to modern science in the 21st century because of their capacity for transmission without an encoding nucleic acid. PrP(Sc), the infectious and alternatively folded form of the PrP prion protein, is capable of self-replication, using PrP(C), the properly folded form of PrP, as a template. This process is associated with neuronal death and the clinical manifestation of prion-based diseases. Unfortunately, little is known about the mechanisms that drive this process. Over the last decade, the theory that a nucleic acid, such as an RNA molecule, might be involved in the process of prion structural conversion has become more widely accepted; such a nucleic acid would act as a catalyst rather than encoding genetic information. Significant amounts of data regarding the interactions of PrP with nucleic acids have created a new foundation for understanding prion conversion and the transmission of prion diseases. Our knowledge has been enhanced by the characterization of a large group of RNA molecules known as non-coding RNAs, which execute a series of important cellular functions, from transcriptional regulation to the modulation of neuroplasticity. The RNA-binding properties of PrP along with the competition with other polyanions, such as glycosaminoglycans and nucleic acid aptamers, open new avenues for therapy.

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Identification and analysis of long‐range electrostatic effects in proteins by computer modeling:aspartate transcarbamylase

Cited by 18 publications

References 0 publications

Optimization of the electrostatic interactions between ionized groups and peptide dipoles in proteins

Optimization of the electrostatic interactions between ionized groups and peptide dipoles in proteins

Electrostatic interactions in the GCN4 leucine zipper: Substantial contributions arise from intramolecular interactions enhanced on binding

The role of RNA in mammalian prion protein conversion

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