Hostname: page-component-76fb5796d-vvkck Total loading time: 0 Render date: 2024-04-26T08:27:22.947Z Has data issue: false hasContentIssue false
  • English
  • Français

Examining Electrostatic Influences on Base-Flipping: A Comparison of TIP3P and GB Solvent Models

Published online by Cambridge University Press:  03 June 2015

Allyn R. Brice  and
Brian N. Dominy
Get access

Abstract

Recently, it was demonstrated that implicit solvent models were capable of generating stable B-form DNA structures. Specifically, generalized Born (GB) implicit solvent models have improved regarding the solvation of conformational sampling of DNA [1,2]. Here, we examine the performance of the GBSW and GBMV models in CHARMM for characterizing base flipping free energy profiles of undamaged and damaged DNA bases. Umbrella sampling of the base flipping process was performed for the bases cytosine, uracil and xanthine. The umbrella sampling simulations were carried-out with both explicit (TIP3P) and implicit (GB) solvent in order to establish the impact of the solvent model on base flipping. Overall, base flipping potential of mean force (PMF) profiles generated with GB solvent resulted in a greater free energy difference of flipping than profiles generated with TIP3P. One of the significant differences between implicit and explicit solvent models is the approximation of solute-solvent interactions in implicit solvent models. We calculated electrostatic interaction energies between explicit water molecules and the base targeted for flipping. These interaction energies were calculated over the base flipping reaction coordinate to illustrate the stabilizing effect of the explicit water molecules on the flipped-out state. It is known that nucleic base pair hydrogen bonds also influenced the free energy of flipping since these favorable interactions must be broken in order for a base to flip-out of the helix. The Watson-Crick base pair hydrogen bond fractions were calculated over the umbrella sampling simulation windows in order to determine the effect of base pair interactions on the base flipping free energy. It is shown that interaction energies between the flipping base and explicit water molecules are responsible for the lower base flipping free energy difference in the explicit solvent PMF profiles.

Keywords

87.15.K-87.15.-vTIP3Pgeneralized Bornflippingimplicit solvationpotential of mean forceDNADNA damage
Type
Research Article
Information
Communications in Computational Physics , Volume 13 , Issue 1 , January 2013 , pp. 223 - 237
Copyright
Copyright © Global Science Press Limited 2013

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

[1]Tsui, V., Case, D.A., Molecular dynamics simulations of nucleic acids with a generalized born solvation model, Journal of the American Chemical Society, 122 (2000) 2489–2498.CrossRefGoogle Scholar
[2]Chocholousova, J., Feig, M., Implicit solvent simulations of DNA and DNA-protein complexes: Agreement with explicit solvent vs experiment, Journal of Physical Chemistry B, 110 (2006) 17240–17251.Google Scholar
[3]Stivers, J.T., Extrahelical damaged base recognition by DNA glycosylase enzymes, Chemistry A European Journal, 14 (2008) 786–793.Google Scholar
[4]Stivers, J.T., Site-specific DNA damage recognition by enzyme-induced base flipping, Progress in Nucleic Acid Research and Molecular Biology, 44 (2004) 37–65.CrossRefGoogle Scholar
[5]Snoussi, K., Leroy, J.L., Imino proton exchange and base-pair kinetics in RNA duplexes, Bio-chemistry, 40 (2001) 8898–8904.Google ScholarPubMed
[6]Berti, PJ., McCann, J.A.B., Toward a detailed understanding of base excision repair enzymes: Transition state and mechanistic analyses of N-glycoside hydrolysis and N-glycoside transfer, Chemical Reviews, 106 (2006) 506–555.Google Scholar
[7]Parker, J.B., Bianchet, M.A., Krosky, D.J., Friedman, J.I., Amzel, L.M., Stivers, J.T., Enzymatic capture of an extrahelical thymine in the search for uracil in DNA, Nature, 449 (2007) 433–438.Google Scholar
[8]Lee, H.W., Brice, A.R., Wright, C.B., Dominy, B.N., Cao, W., Identification of escherichia coli mismatch-specific uracil DNA glycosylase as a robust xanthine DNA glycosylase, Journal of Biological Chemistry, 285 (2010) 41483–41490.Google Scholar
[9]Priyakumar, U.D., MacKerell, A.D., Computational approaches for investigating base flipping in oligonucleotides, Chemical Reviews, 106 (2006) 489–505.Google Scholar
[10]Torrie, G.M., Valleau, J.P., Monte-Carlo study of a phase-separating liquid-mixture by umbrella sampling, Journal of Chemical Physics, 66 (1977) 1402–1408.Google Scholar
[11]Kollman, P., Free-energy calculations: Applications to chemical and biochemical phenomena, Chemical Reviews, 93 (1993) 2395–2417.CrossRefGoogle Scholar
[12]Banavali, N., Mackerell, A.D. Jr., Free energy and structural pathways of base flipping in a DNA GCGC containing sequence, Journal of Molecular Biology, 319 (2002) 141–160.Google Scholar
[13]Song, K., Campbell, A.J., Bergonzo, C., Santos, C., Grollman, A.P., Simmerling, C., An improved reaction coordinate for nucleic acid base flipping studies, Journal of Chemical Theory and Computation, 5 (2009) 3105–3113.Google Scholar
[14]Priyakumar, U.D., Mackerell, A.D. Jr., Computational approaches for investigating base flipping in oligonucleotides, Chemical Reviews, 106 (2006) 489–505.Google Scholar
[15]Cheatham, T.E., Kollman, P.A., Molecular dynamics simulation of nucleic acids, Annual Review of Physical Chemistry, 51 (2000) 435–471.Google Scholar
[16]Norberg, J., Nilsson, L., Molecular dynamics applied to nucleic acids, Accounts of Chemical Research, 35 (2002) 465–472.Google Scholar
[17]Priyakumar, U.D., Mackerell, A.D. Jr., Base flipping in a GCGC Containing DNA Dodecamer: A comparative study of the performance of the nucleic acid force fields, CHARMM, AMBER, and BMS, Journal of Chemical Theory and Computation, 2 (2006) 187–200.CrossRefGoogle Scholar
[18]MacKerell, A.D., Banavali, N.K., All-atom empirical force field for nucleic acids: II. Application to molecular dynamics simulations of DNA and RNA in solution, Journal of Computational Chemistry, 21 (2000) 105–120.Google Scholar
[19]Cheatham, T.E., Cieplak, P., Kollman, P.A., A modified version of the Cornell et al. force field with improved sugar pucker phases and helical repeat, Journal of Biomolecular Structure and Dynamics, 16 (1999) 845–862.Google Scholar
[20]Langley, D.R., Molecular dynamic simulations of environment and sequence dependent DNA conformations: The development of the BMS nucleic acid force field and comparison with experimental results, Journal of Biomolecular Structure and Dynamics, 16 (1998) 487–509.Google Scholar
[21]Foloppe, N., Mackerell, A.D. Jr., All-atom empirical force field for nucleic acids: I. Parameter optimization based on small molecule and condensed phase macromolecular target data, Journal of Computational Chemistry, 21 (1999) 86–104.Google Scholar
[22]Dornberger, U., Leijon, M., Fritzsche, H., High base pair opening rates in tracts of GC base pairs, Journal of Biological Chemistry, 274 (1999) 6957–6962.Google Scholar
[23]Cheatham, T.E., Crowley, M.F., Kollman, P.A., A molecular level picture of the stabilization of A-DNA in mixed ethanol-water solutions, Proceedings of the National Academy of Sciences of the United States of America, 94 (1997) 9626–9630.Google Scholar
[24]Feig, M., Chocholousova, J., Tanizaki, S., Extending the horizon: Towards the efficient modeling of large biomolecular complexes in atomic detail, Theoretical Chemistry Accounts, 116 (2006) 194–205.CrossRefGoogle Scholar
[25]Sands, Z.A., Laughton, C.A., Molecular dynamics simulations of DNA using the generalized born solvation model: Quantitative comparisons with explicit solvation results, Journal of Physical Chemistry B, 108 (2004) 10113–10119.CrossRefGoogle Scholar
[26]Feig, M., Brooks, C.L., Recent advances in the development and application of implicit solvent models in biomolecule simulations, Current Opinion in Structural Biology, 14 (2004) 217–224.Google Scholar
[27]Dominy, B.N., Brooks, C.L., Development of a generalized born model parametrization for proteins and nucleic acids, Journal of Physical Chemistry B, 103 (1999) 3765–3773.Google Scholar
[28]Roux, B., Simonson, T., Implicit solvent models, Biophysical Chemistry, 78 (1999) 1–20.Google Scholar
[29]Ooi, T., Obatake, M., Nemethy, G., Scheraga, H.A., Accessible surface areas as a measure of the thermodynamic parameters of hydration of peptides, Proceedings of the National Academy of Sciences of The United States of America, 84 (1987) 3083–3090.Google ScholarPubMed
[30]McConnell, K.J., Beveridge, D.L., DNA Structure: What’s in charge?, Journal of Molecular Biology, 304 (2000) 803–820.Google Scholar
[31]Sharp, K.A., Honig, B., Electrostatic interactions in macromolecules: Theory and applications, Annual Review of Biophysics and Biophysical Chemistry, 19 (1990) 301–332.Google Scholar
[32]Boschitsch, A.H., Fenley, M.O., Zhou, H.X., Fast boundary element method for the linear Poisson-Boltzmann equation, Journal of Physical Chemistry B, 106 (2002) 2741–2754.Google Scholar
[33]Holst, M., Baker, N., Wang, F., Adaptive multilevel finite element solution of the Poisson-Boltzmann equation I. Algorithms and examples, Journal of Computational Chemistry, 21 (2000) 1319–1342.Google Scholar
[34]Zimm, B.H., Lebret, M., Counterion condensation and system dimensionality, Journal of Biomolecular Structure and Dynamics, 1 (1983) 461–471.Google Scholar
[35]Born, M., Volumen und hydratationswarme der ionen, Z. Phys., 1 (1920) 45–48.CrossRefGoogle Scholar
[36]Still, W.C., Tempczyk, A., Hawley, R.C., Hendrickson, T., Semianalytical treatment of solvation for molecular mechanics and dynamics, Journal of the American Chemical Society, 112 (1990) 6127–6129.Google Scholar
[37]Srinivasan, J., Trevathan, M.W., Beroza, P., Case, D.A., Applications of a pairwise generalized born model to proteins and nucleic acids: Inclusion of salt effect, Theoretical Chemistry Accounts, 101 (1999) 426–434.Google Scholar
[38]Im, W., Lee, M.S., Brooks, C.L., Generalized born model with a simple smoothing function, Journal of Computational Chemistry, 24 (2003) 1691–1702.Google Scholar
[39]Lee, M.S., Feig, M., Salsbury, F.R., Brooks, C.L., New analytic approximation to the standard molecular volume definition and its application to generalized born calculations, Journal of Computational Chemistry, 24 (2003) 1348–1356.Google Scholar
[40]Banavali, N., Roux, B., Atomic radii for continuum electrostatic calculations on nucleic acids, Journal of Physical Chemistry B, 106 (2002) 11026–11035.Google Scholar
[41]Srinivasan, J., Cheatham, T.E., Cieplak, P., Kollman, P.A., Case, D.A., Continuum Solvent studies of the stability of DNA, RNA, and phosphoramidate – DNA helices, Journal of the American Chemical Society, 120 (1998) 9401–9409.Google Scholar
[42]Brice, A.R., Dominy, B.N., Analyzing the robustness of the MM/PBSA free energy calculation method: Application to DNA conformational transitions, Journal of Computational Chemistry, 32 (2011) 1431–1440.Google Scholar
[43]MacKerell, A.D., Bashford, D., Bellott, M., Dunbrack, R.L., Evanseck, J.D., Field, M.J., Fischer, S., Gao, J., Guo, H., Ha, S., Joseph-McCarthy, D., Kuchnir, L., Kuczera, K., Lau, F.T.K., Mattos, C., Michnick, S., Ngo, T., Nguyen, D.T., Prodhom, B., Reiher, W.E., Roux, B., Schlenkrich, M., Smith, J.C., Stote, R., Straub, J., Watanabe, M., Wiorkiewicz-Kuczera, J., Yin, D., Karplus, M., Allatom empirical potential for molecular modeling and dynamics studies of proteins, Journal of Physical Chemistry B, 102 (1998) 3586–3616.Google Scholar
[44]Lu, X.J., Olson, W.K., 3DNA: A software package for the analysis, rebuilding and visualization of three-dimensional nucleic acid structures, Nucleic Acids Research, 31 (2003) 5108–5121.Google Scholar
[45]Chocholousova, J., Feig, M., Balancing an accurate representation of the molecular surface in generalized born formalisms with integrator stability in molecular dynamics simulations, Journal of Computational Chemistry, 27 (2005) 719–729.Google Scholar
[46]Darden, T., York, D., Pedersen, L.J., Particle mesh Ewald: An N-log(N) method for Ewald sums in large systems, Journal of Chemical Physics, 98 (1993) 10089.CrossRefGoogle Scholar
[47]Kumar, S., Bouzida, D., Swendsen, R.H., Kollman, P.A., Rosenberg, J.M., The weighted histogram analysis method for free-energy calculations on biomolecules. I. The method, Journal of Computational Chemistry, 13 (1992) 1011–1021.Google Scholar
[48]Feig, M., Onufriev, A., Lee, M.S., Im, W., Case, D.A., Brooks, C.L., Performance comparison of generalized born and Poisson methods in the calculation of electrostatic solvation energies for protein structures, Journal of Computational Chemistry, 25 (2003) 265–284.Google Scholar
[49]Simonson, T., Macromolecular electrostatics: Continuum models and their growing pains, Current Opinion in Structural Biology, 11 (2001) 243–252.Google Scholar