SIRAH: a structurally unbiased coarse-grained force field for proteins with aqueous solvation and long-range electrostatics.

Modeling of macromolecular structures and interactions represents an important challenge for computational biology, involving different time and length scales. However, this task can be facilitated through the use of coarse-grained (CG) models, which reduce the number of degrees of freedom and allow efficient exploration of complex conformational spaces. This article presents a new CG protein model named SIRAH, developed to work with explicit solvent and to capture sequence, temperature, and ionic strength effects in a topologically unbiased manner. SIRAH is implemented in GROMACS, and interactions are calculated using a standard pairwise Hamiltonian for classical molecular dynamics simulations. We present a set of simulations that test the capability of SIRAH to produce a qualitatively correct solvation on different amino acids, hydrophilic/hydrophobic interactions, and long-range electrostatic recognition leading to spontaneous association of unstructured peptides and stable structures of single polypeptides and protein-protein complexes.

[1]  Nathan A. Baker,et al.  Electrostatics of nanosystems: Application to microtubules and the ribosome , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[2]  Ernest D Laue,et al.  Structural basis of HP1/PXVXL motif peptide interactions and HP1 localisation to heterochromatin , 2004, The EMBO journal.

[3]  Alexey Savelyev,et al.  Chemically accurate coarse graining of double-stranded DNA , 2010, Proceedings of the National Academy of Sciences.

[4]  Daniel Borgis,et al.  Modeling Protein-Protein Recognition in Solution Using the Coarse-Grained Force Field SCORPION. , 2013, Journal of chemical theory and computation.

[5]  Siewert J Marrink,et al.  Martini Coarse-Grained Force Field: Extension to Carbohydrates. , 2009, Journal of chemical theory and computation.

[6]  David D. Thomas,et al.  Solid-state NMR and rigid body molecular dynamics to determine domain orientations of monomeric phospholamban. , 2002, Journal of the American Chemical Society.

[7]  Pawel Sikorski,et al.  Molecular basis for amyloid fibril formation and stability. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[8]  Klaus Schulten,et al.  Four-scale description of membrane sculpting by BAR domains. , 2008, Biophysical journal.

[9]  V. Hornak,et al.  Comparison of multiple Amber force fields and development of improved protein backbone parameters , 2006, Proteins.

[10]  T. Südhof,et al.  Three-Dimensional Structure of the Complexin/SNARE Complex , 2002, Neuron.

[11]  M. Sansom,et al.  Coarse-grained simulation: a high-throughput computational approach to membrane proteins. , 2008, Biochemical Society transactions.

[12]  E. Atkins,et al.  "Cross-beta" conformation in proteins. , 1968, Journal of molecular biology.

[13]  K. Bailey,et al.  The X-ray interpretation of denaturation and the structure of the seed globulins. , 1935, The Biochemical journal.

[14]  Ernesto T. A. Marques,et al.  Influence of Scaffold Stability and Electrostatics on Top7-Based Engineered Helical HIV-1 Epitopes , 2013, BSB.

[15]  Marilisa Neri,et al.  Coarse-grained model of proteins incorporating atomistic detail of the active site. , 2005, Physical review letters.

[16]  E. Atkins,et al.  “Cross-β” conformation in proteins☆ , 1968 .

[17]  Tristan Bereau,et al.  Generic coarse-grained model for protein folding and aggregation. , 2009, The Journal of chemical physics.

[18]  Marc Baaden,et al.  Mixing Atomistic and Coarse Grain Solvation Models for MD Simulations: Let WT4 Handle the Bulk. , 2012, Journal of chemical theory and computation.

[19]  Leonardo Darré,et al.  Transferable mixing of atomistic and coarse-grained water models. , 2013, The journal of physical chemistry. B.

[20]  Susan S. Taylor,et al.  Classification and Phylogenetic Analysis of the cAMP-Dependent Protein Kinase Regulatory Subunit Family , 2002, Journal of Molecular Evolution.

[21]  P. Cuatrecasas,et al.  AMYLOID. VI. A COMPARISON OF TWO MORPHOLOGIC COMPONENTS OF HUMAN AMYLOID DEPOSITS , 1968, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[22]  S. Pantano,et al.  A hybrid all-atom/coarse grain model for multiscale simulations of DNA. , 2011, Physical chemistry chemical physics : PCCP.

[23]  S. Elgin,et al.  Heterochromatin Protein 1a (HP1a) Partner Specificity Is Determined by Critical Amino Acids in the Chromo Shadow Domain and C-terminal Extension* , 2013, The Journal of Biological Chemistry.

[24]  Ilpo Vattulainen,et al.  Multiscale modeling of emergent materials: biological and soft matter. , 2009, Physical chemistry chemical physics : PCCP.

[25]  T. Südhof,et al.  Membrane Fusion: Grappling with SNARE and SM Proteins , 2009, Science.

[26]  Sergio Pantano,et al.  A Coarse Grained Model for Atomic-Detailed DNA Simulations with Explicit Electrostatics. , 2010, Journal of chemical theory and computation.

[27]  A. Stewart,et al.  The chromo shadow domain, a second chromo domain in heterochromatin-binding protein 1, HP1. , 1995, Nucleic acids research.

[28]  Klaus Schulten,et al.  Further optimization of a hybrid united-atom and coarse-grained force field for folding simulations: Improved backbone hydration and interactions between charged side chains. , 2012, Journal of chemical theory and computation.

[29]  Paolo Carloni,et al.  Catabolite activator protein in aqueous solution: a molecular simulation study. , 2007, The journal of physical chemistry. B.

[30]  R J Mortishire-Smith,et al.  Solution structure of the cytoplasmic domain of phopholamban: phosphorylation leads to a local perturbation in secondary structure. , 1995, Biochemistry.

[31]  W G Noid,et al.  Perspective: Coarse-grained models for biomolecular systems. , 2013, The Journal of chemical physics.

[32]  Kurt Kremer,et al.  Simulation of polymer melts. I. Coarse‐graining procedure for polycarbonates , 1998 .

[33]  Susan S. Taylor,et al.  The cAMP binding domain: an ancient signaling module. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[34]  Helgi I Ingólfsson,et al.  The power of coarse graining in biomolecular simulations , 2013, Wiley interdisciplinary reviews. Computational molecular science.

[35]  Wataru Shinoda,et al.  Large-Scale Molecular Dynamics Simulations of Self-Assembling Systems , 2008, Science.

[36]  Michele Cascella,et al.  Electrostatic-Consistent Coarse-Grained Potentials for Molecular Simulations of Proteins. , 2013, Journal of chemical theory and computation.

[37]  L. Jones,et al.  Phospholamban: protein structure, mechanism of action, and role in cardiac function. , 1998, Physiological reviews.

[38]  Marc Baaden,et al.  The OPEP protein model: from single molecules, amyloid formation, crowding and hydrodynamics to DNA/RNA systems. , 2014, Chemical Society reviews.

[39]  Pablo D. Dans,et al.  Another Coarse Grain Model for Aqueous Solvation: WAT FOUR? , 2010 .

[40]  Jan H. Jensen,et al.  Very fast empirical prediction and rationalization of protein pKa values , 2005, Proteins.

[41]  L. Reymond,et al.  Intramolecular distances and dynamics from the combined photon statistics of single-molecule FRET and photoinduced electron transfer. , 2013, The journal of physical chemistry. B.

[42]  T. Darden,et al.  Particle mesh Ewald: An N⋅log(N) method for Ewald sums in large systems , 1993 .

[43]  E. Laue,et al.  Structural basis of HP 1 / PXVXL motif peptide interactions and HP 1 localisation to heterochromatin , 2013 .

[44]  Jonathan W. Essex,et al.  The ELBA Force Field for Coarse-Grain Modeling of Lipid Membranes , 2011, PloS one.

[45]  D. Baker,et al.  Design of a Novel Globular Protein Fold with Atomic-Level Accuracy , 2003, Science.

[46]  S. Pantano,et al.  Breathing, bubbling, and bending: DNA flexibility from multimicrosecond simulations. , 2012, Physical review. E, Statistical, nonlinear, and soft matter physics.

[47]  Nathan A. Baker,et al.  PDB2PQR: an automated pipeline for the setup of Poisson-Boltzmann electrostatics calculations , 2004, Nucleic Acids Res..

[48]  O. Lange,et al.  A Mechanism for the Auto-inhibition of Hyperpolarization-activated Cyclic Nucleotide-gated (HCN) Channel Opening and Its Relief by cAMP* , 2014, The Journal of Biological Chemistry.

[49]  S. Pantano,et al.  The blockade of the neurotransmitter release apparatus by botulinum neurotoxins , 2013, Cellular and Molecular Life Sciences.

[50]  M. Parrinello,et al.  Polymorphic transitions in single crystals: A new molecular dynamics method , 1981 .

[51]  M. Parrinello,et al.  Canonical sampling through velocity rescaling. , 2007, The Journal of chemical physics.

[52]  S. Pantano,et al.  cAMP Modulation of the cytoplasmic domain in the HCN2 channel investigated by molecular simulations. , 2006, Biophysical journal.

[53]  Reinhard Jahn,et al.  SNAREs — engines for membrane fusion , 2006, Nature Reviews Molecular Cell Biology.

[54]  R. Larson,et al.  The MARTINI Coarse-Grained Force Field: Extension to Proteins. , 2008, Journal of chemical theory and computation.

[55]  G. Voth.  Coarse-Graining of Condensed Phase and Biomolecular Systems , 2008 .

[56]  Joanna Trylska,et al.  HIV-1 protease substrate binding and product release pathways explored with coarse-grained molecular dynamics. , 2007, Biophysical journal.

[57]  Matías R. Machado,et al.  Coarse‐grained models of water , 2012 .

[58]  Sergio Pantano,et al.  Assessing the Accuracy of the SIRAH Force Field to Model DNA at Coarse Grain Level , 2013, BSB.

[59]  R. Lavery,et al.  PaLaCe: A Coarse-Grain Protein Model for Studying Mechanical Properties. , 2013, Journal of chemical theory and computation.

[60]  Antonio Trovato,et al.  Optimal shapes of compact strings , 2000, Nature.

[61]  S. Pantano,et al.  The role of phosphorylation on the structure and dynamics of phospholamban: A model from molecular simulations , 2006, Proteins.

[62]  D. Tieleman,et al.  The MARTINI force field: coarse grained model for biomolecular simulations. , 2007, The journal of physical chemistry. B.

[63]  Adam K. Sieradzan,et al.  Revised Backbone-Virtual-Bond-Angle Potentials to Treat the l- and d-Amino Acid Residues in the Coarse-Grained United Residue (UNRES) Force Field , 2014, Journal of chemical theory and computation.

[64]  Pritam Ganguly,et al.  Systematic coarse-graining methods for soft matter simulations - a review , 2013 .

[65]  Leonor Saiz,et al.  Computer simulation studies of model biological membranes. , 2002, Accounts of chemical research.