Marta Filizola

Summary

Affiliation: Mount Sinai School of Medicine
Country: USA

Publications

  1. pmc Lessons from free energy simulations of delta-opioid receptor homodimers involving the fourth transmembrane helix
    Davide Provasi
    Department of Structural and Chemical Biology, Mount Sinai School of Medicine, New York, New York 10029, USA
    Biochemistry 49:6771-6. 2010
  2. pmc Making structural sense of dimerization interfaces of delta opioid receptor homodimers
    Jennifer M Johnston
    Department of Structural and Chemical Biology, Mount Sinai School of Medicine, New York, New York 10029, United States
    Biochemistry 50:1682-90. 2011
  3. pmc Ligand-induced modulation of the free-energy landscape of G protein-coupled receptors explored by adaptive biasing techniques
    Davide Provasi
    Department of Structural and Chemical Biology, Mount Sinai School of Medicine, New York, New York, United States of America
    PLoS Comput Biol 7:e1002193. 2011
  4. pmc Grand opening of structure-guided design for novel opioids
    Marta Filizola
    Department of Structural and Chemical Biology, Mount Sinai School of Medicine, New York, NY 10029, USA
    Trends Pharmacol Sci 34:6-12. 2013
  5. pmc Increasingly accurate dynamic molecular models of G-protein coupled receptor oligomers: Panacea or Pandora's box for novel drug discovery?
    Marta Filizola
    Department of Structural and Chemical Biology, Mount Sinai School of Medicine, Icahn Medical Institute Building, 1425 Madison Avenue, Box 1677, New York, NY 10029 6574, United States
    Life Sci 86:590-7. 2010
  6. pmc Effects of limiting extension at the alphaIIb genu on ligand binding to integrin alphaIIbbeta3
    Robert Blue
    Laboratory of Blood and Vascular Biology, The Rockefeller University, New York, New York 10021, USA
    J Biol Chem 285:17604-13. 2010
  7. pmc Dopamine D2 receptors form higher order oligomers at physiological expression levels
    Wen Guo
    Center for Molecular Recognition, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA
    EMBO J 27:2293-304. 2008
  8. pmc Functional and computational studies of the ligand-associated metal binding site of beta3 integrins
    Marta Murcia
    Department of Structural and Chemical Biology, Mount Sinai School of Medicine, New York, New York 10029 6574, USA
    Proteins 71:1779-91. 2008
  9. pmc Putative active states of a prototypic g-protein-coupled receptor from biased molecular dynamics
    Davide Provasi
    Department of Structural and Chemical Biology, Mount Sinai School of Medicine, New York, New York, USA
    Biophys J 98:2347-55. 2010
  10. pmc Modern homology modeling of G-protein coupled receptors: which structural template to use?
    Juan Carlos Mobarec
    Department of Structural and Chemical Biology, Mount Sinai School of Medicine, 1425 Madison Avenue, Box 1677, New York, NY 10029 6574, USA
    J Med Chem 52:5207-16. 2009

Collaborators

Detail Information

Publications38

  1. pmc Lessons from free energy simulations of delta-opioid receptor homodimers involving the fourth transmembrane helix
    Davide Provasi
    Department of Structural and Chemical Biology, Mount Sinai School of Medicine, New York, New York 10029, USA
    Biochemistry 49:6771-6. 2010
    ..The results of these simulations, combined with estimates of diffusion-limited association rates, suggest a short lifetime for deltaOR homodimers in the membrane, in agreement with recent trends...
  2. pmc Making structural sense of dimerization interfaces of delta opioid receptor homodimers
    Jennifer M Johnston
    Department of Structural and Chemical Biology, Mount Sinai School of Medicine, New York, New York 10029, United States
    Biochemistry 50:1682-90. 2011
    ..Additional CG umbrella sampling simulations of the 4/5 dimer indicated that the strength of association between DOR protomers varies depending on the protein region at the interface, with the 4 dimer being more stable than the 4/5 dimer...
  3. pmc Ligand-induced modulation of the free-energy landscape of G protein-coupled receptors explored by adaptive biasing techniques
    Davide Provasi
    Department of Structural and Chemical Biology, Mount Sinai School of Medicine, New York, New York, United States of America
    PLoS Comput Biol 7:e1002193. 2011
    ..Structural inspection of these metastable states reveals unique conformations of the receptor that may have been difficult to retrieve experimentally...
  4. pmc Grand opening of structure-guided design for novel opioids
    Marta Filizola
    Department of Structural and Chemical Biology, Mount Sinai School of Medicine, New York, NY 10029, USA
    Trends Pharmacol Sci 34:6-12. 2013
    ....
  5. pmc Increasingly accurate dynamic molecular models of G-protein coupled receptor oligomers: Panacea or Pandora's box for novel drug discovery?
    Marta Filizola
    Department of Structural and Chemical Biology, Mount Sinai School of Medicine, Icahn Medical Institute Building, 1425 Madison Avenue, Box 1677, New York, NY 10029 6574, United States
    Life Sci 86:590-7. 2010
    ..e. more potent and selective drugs for efficient therapeutic interventions...
  6. pmc Effects of limiting extension at the alphaIIb genu on ligand binding to integrin alphaIIbbeta3
    Robert Blue
    Laboratory of Blood and Vascular Biology, The Rockefeller University, New York, New York 10021, USA
    J Biol Chem 285:17604-13. 2010
    ..Our data are consistent with alphaIIb extension resulting in increased access to the ligand-binding site and/or facilitating the conformational change(s) in beta3 that affect the intrinsic affinity of the binding pocket for ligand...
  7. pmc Dopamine D2 receptors form higher order oligomers at physiological expression levels
    Wen Guo
    Center for Molecular Recognition, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA
    EMBO J 27:2293-304. 2008
    ..Thus, at physiological levels of expression, the receptor is organized in the plasma membrane into a higher order oligomeric structure...
  8. pmc Functional and computational studies of the ligand-associated metal binding site of beta3 integrins
    Marta Murcia
    Department of Structural and Chemical Biology, Mount Sinai School of Medicine, New York, New York 10029 6574, USA
    Proteins 71:1779-91. 2008
    ..Our computational results indicate that the LIMBS plays a crucial role in ligand binding to alphaIIbeta3 by virtue of its effects on the coordination of the MIDAS...
  9. pmc Putative active states of a prototypic g-protein-coupled receptor from biased molecular dynamics
    Davide Provasi
    Department of Structural and Chemical Biology, Mount Sinai School of Medicine, New York, New York, USA
    Biophys J 98:2347-55. 2010
    ....
  10. pmc Modern homology modeling of G-protein coupled receptors: which structural template to use?
    Juan Carlos Mobarec
    Department of Structural and Chemical Biology, Mount Sinai School of Medicine, 1425 Madison Avenue, Box 1677, New York, NY 10029 6574, USA
    J Med Chem 52:5207-16. 2009
    ....
  11. pmc Targeted molecular dynamics reveals overall common conformational changes upon hybrid domain swing-out in beta3 integrins
    Davide Provasi
    Department of Structural and Chemical Biology, Mount Sinai School of Medicine, New York, NY 10029 6574, USA
    Proteins 77:477-89. 2009
    ..Taken together, our results suggest novel testable hypotheses of intradomain and interdomain interactions responsible for beta3 integrin activation...
  12. pmc Structural and therapeutic insights from the species specificity and in vivo antithrombotic activity of a novel alphaIIb-specific alphaIIbbeta3 antagonist
    Robert Blue
    Laboratory of Blood and Vascular Biology, Rockefeller University, New York, NY 10065, USA
    Blood 114:195-201. 2009
    ..Collectively, these data support RUC-1's specificity for alphaIIb, provide new insights into the alphaIIb binding pocket, and establish RUC-1's antithrombotic effects in vivo...
  13. pmc Assessing the relative stability of dimer interfaces in g protein-coupled receptors
    Jennifer M Johnston
    Department of Structural and Chemical Biology, Mount Sinai School of Medicine, New York, New York, United States of America
    PLoS Comput Biol 8:e1002649. 2012
    ....
  14. pmc Dynamic models of G-protein coupled receptor dimers: indications of asymmetry in the rhodopsin dimer from molecular dynamics simulations in a POPC bilayer
    Marta Filizola
    Department of Physiology and Biophysics, Weill Medical College of Cornell University, 1300 York Ave, New York, NY 10021, USA
    J Comput Aided Mol Des 20:405-16. 2006
    ..The results are consistent with a model of GPCR activation that involves allosteric modulation through a single GPCR subunit per dimer...
  15. pmc Exploring molecular mechanisms of ligand recognition by opioid receptors with metadynamics
    Davide Provasi
    Department of Structural and Chemical Biology, Mount Sinai School of Medicine, New York, New York 10029, USA
    Biochemistry 48:10020-9. 2009
    ..The strategy employed herein holds promise for its application to the docking of diverse ligands to the opioid receptors as well as to other GPCRs...
  16. pmc Structure-based virtual screening of small-molecule antagonists of platelet integrin αIIbβ3 that do not prime the receptor to bind ligand
    Ana Negri
    Department of Structural and Chemical Biology, Mount Sinai School of Medicine, 1425 Madison Avenue, Box 1677, New York, NY 10029 6574, USA
    J Comput Aided Mol Des 26:1005-15. 2012
    ..The newly identified compounds, like RUC-1 and RUC-2, showed specificity for αIIbβ3 compared to αVβ3 and did not prime the receptor to bind ligand. They thus may hold promise as αIIbβ3 antagonist therapeutic scaffolds...
  17. pmc Influence of oligomerization on the dynamics of G-protein coupled receptors as assessed by normal mode analysis
    Masha Y Niv
    Department of Physiology and Biophysics, Weill Medical College of Cornell University, New York, NY, USA
    Proteins 71:575-86. 2008
    ....
  18. pmc GPCR-OKB: the G Protein Coupled Receptor Oligomer Knowledge Base
    George Khelashvili
    Department of Physiology and Biophysics, Weill Medical College of Cornell University, New York, NY, USA
    Bioinformatics 26:1804-5. 2010
    ..Such data were manually derived from the literature. While focused on GPCR oligomers, GPCR-OKB is seamlessly connected to GPCRDB, facilitating the correlation of information about GPCR protomers and oligomers...
  19. ncbi request reprint TRAJELIX: a computational tool for the geometric characterization of protein helices during molecular dynamics simulations
    Mihaly Mezei
    Department of Physiology and Biophysics, Mount Sinai School of Medicine, NYU, One Gustave L Levy Place, Box 1218, New York, NY 10029, USA
    J Comput Aided Mol Des 20:97-107. 2006
    ..Quantification of the dynamic structural behavior of alpha-helical membrane proteins is critical for our understanding of signal transduction, and may enable structure-based design of more specific and efficient drugs...
  20. pmc Molecular determinants and thermodynamics of the amyloid precursor protein transmembrane domain implicated in Alzheimer's disease
    Hao Wang
    Department of Structural and Chemical Biology, Mount Sinai School of Medicine, One Gustave L Levy Place, New York, NY 10029, USA
    J Mol Biol 408:879-95. 2011
    ..This observation might have important biological implications, since dimers with a different arrangement of the transmembrane helices are likely to be recognized differently by γ-secretase and to lead to a variation in Aβ levels...
  21. ncbi request reprint Mechanistic insights from a refined three-dimensional model of integrin alphaIIbbeta3
    Marta Filizola
    Department of Physiology and Biophysics, Weill Medical College of Cornell University, New York, New York 10021, USA
    J Biol Chem 279:24624-30. 2004
    ..In addition, it suggests mechanistic hypotheses pertaining to both naturally occurring mutations responsible for Glanzmann thrombasthenia and to point mutations that affect ligand binding...
  22. pmc Membrane driven spatial organization of GPCRs
    Sayan Mondal
    Department of Physiology and Biophysics, Weill Cornell Medical College of Cornell University, New York, New York 10065, United States
    Sci Rep 3:2909. 2013
    ..The results provide a mechanistic understanding of the structural context of oligomerization. ..
  23. ncbi request reprint The structure and dynamics of GPCR oligomers: a new focus in models of cell-signaling mechanisms and drug design
    Marta Filizola
    Weill Medical College of Cornell University, Department of Physiology and Biophysics, New York, NY 10021, USA
    Curr Opin Drug Discov Devel 8:577-84. 2005
    ..The development of increasingly accurate dynamic molecular models of GPCR dimers is expected to produce a more complete structural context for understanding the molecular mechanisms of GPCR function, and to aid in drug discovery...
  24. ncbi request reprint Prediction of heterodimerization interfaces of G-protein coupled receptors with a new subtractive correlated mutation method
    Marta Filizola
    Department of Physiology and Biophysics, Mount Sinai School of Medicine, One Gustave Levy Place, New York, NY 10029, USA
    Protein Eng 15:881-5. 2002
    ..However, in the absence of a known structure of any GPCR dimer, the features of the method and predictions are also illustrated and analyzed for a dimeric complex of known structure...
  25. pmc Beyond standard molecular dynamics: investigating the molecular mechanisms of G protein-coupled receptors with enhanced molecular dynamics methods
    Jennifer M Johnston
    Department of Structural and Chemical Biology, Icahn School of Medicine at Mount Sinai, One Gustave L Levy Place, New York, NY, 10029, USA
    Adv Exp Med Biol 796:95-125. 2014
    ..We provide here an overview of these methods in their most recent application to the field. ..
  26. pmc Crosstalk in G protein-coupled receptors: changes at the transmembrane homodimer interface determine activation
    Wen Guo
    Center for Molecular Recognition, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA
    Proc Natl Acad Sci U S A 102:17495-500. 2005
    ..Thus, a conformational change at the TM4 dimer interface is part of the receptor activation mechanism...
  27. pmc Inward-facing conformation of the zinc transporter YiiP revealed by cryoelectron microscopy
    Nicolas Coudray
    Laboratory of Cryo Electron Microscopy, New York Structural Biology Center, New York, NY 10027, USA
    Proc Natl Acad Sci U S A 110:2140-5. 2013
    ..Association of the C-terminal domains is the same in both states, and we speculate that this association is responsible for stabilizing the dimer that, in turn, may coordinate the rearrangement of the transmembrane helices...
  28. pmc Modeling activated states of GPCRs: the rhodopsin template
    Masha Y Niv
    Department of Physiology and Biophysics, Weill Medical College of Cornell University, 1300 York Ave, New York, NY 10021, USA
    J Comput Aided Mol Des 20:437-48. 2006
    ..This result may differentiate rhodopsin from other GPCRs, and the reasons for this difference are discussed in the context of the structural properties and the physiological function of the protein...
  29. pmc Decoding the signaling of a GPCR heteromeric complex reveals a unifying mechanism of action of antipsychotic drugs
    Miguel Fribourg
    Department of Structural and Chemical Biology, Mount Sinai School of Medicine, New York, NY 10029, USA
    Cell 147:1011-23. 2011
    ..These observations provide mechanistic insight into antipsychotic action that may advance therapeutic strategies for disorders including schizophrenia and dementia...
  30. pmc Discovery of a novel selective kappa-opioid receptor agonist using crystal structure-based virtual screening
    Ana Negri
    Department of Structural and Chemical Biology, Icahn School of Medicine at Mount Sinai, New York, New York 10029, United States
    J Chem Inf Model 53:521-6. 2013
    ..A selective novel KOP receptor agonist emerged as a notable result and is proposed as a new chemotype for the study of the KOP receptor in the etiology of drug addiction, depression, and/or pain...
  31. ncbi request reprint Structural models for dimerization of G-protein coupled receptors: the opioid receptor homodimers
    Marta Filizola
    Department of Physiology and Biophysics, Mount Sinai School of Medicine, One Gustave L Levy Place, New York, NY 10029, USA
    Biopolymers 66:317-25. 2002
    ..The approach is illustrated for the three cloned opioid receptor subtypes (OPRD, OPRM, and OPRK)...
  32. pmc Bioactive conformations of two seminal delta opioid receptor penta-peptides inferred from free-energy profiles
    Guido Scarabelli
    Department of Structural and Chemical Biology, Icahn School of Medicine at Mount Sinai, New York, NY
    Biopolymers 101:21-7. 2014
    ..Candidate bioactive forms of these peptides are selected from identified common spatial arrangements of key pharmacophoric points within all sampled conformations. © 2013 Wiley Periodicals, Inc. Biopolymers 101: 21-27, 2014. ..
  33. pmc Identification of a serotonin/glutamate receptor complex implicated in psychosis
    Javier Gonzalez-Maeso
    Department of Neurology, Mount Sinai School of Medicine, New York, New York 10029, USA
    Nature 452:93-7. 2008
    ..These regulatory changes indicate that the 2AR-mGluR2 complex may be involved in the altered cortical processes of schizophrenia, and this complex is therefore a promising new target for the treatment of psychosis...
  34. pmc Identification of a μ-δ opioid receptor heteromer-biased agonist with antinociceptive activity
    Ivone Gomes
    Department of Pharmacology and Systems Therapeutics, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
    Proc Natl Acad Sci U S A 110:12072-7. 2013
    ....
  35. pmc Requirements and ontology for a G protein-coupled receptor oligomerization knowledge base
    Lucy Skrabanek
    Department of Physiology and Biophysics, Weill Medical College of Cornell University, New York, NY, USA
    BMC Bioinformatics 8:177. 2007
    ....
  36. pmc Showcasing modern molecular dynamics simulations of membrane proteins through G protein-coupled receptors
    Jennifer M Johnston
    Department of Structural and Chemical Biology, Mount Sinai School of Medicine, 1425 Madison Avenue, Box 1677, New York, NY 10029, USA
    Curr Opin Struct Biol 21:552-8. 2011
    ..We provide here a concise overview of recent developments in computational biophysics of membrane proteins, using GPCRs as an example to showcase important information that can be derived from modern MD simulations...
  37. pmc Differential stability of the crystallographic interfaces of mu- and kappa-opioid receptors
    Jennifer M Johnston
    Department of Structural and Chemical Biology, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America
    PLoS ONE 9:e90694. 2014
    ..This information can be used to guide experiments aimed at exploring the role of dimerization in opioid receptor function. ..
  38. ncbi request reprint Progress in elucidating the structural and dynamic character of G Protein-Coupled Receptor oligomers for use in drug discovery
    A Bortolato
    Department of Structural and Chemical Biology, Mount Sinai School of Medicine, New York, NY 10029 6574, USA
    Curr Pharm Des 15:4017-25. 2009
    ....

Research Grants6

  1. OPIOID RECEPTOR OLIGOMERIZATION: PREDICTION & VALIDATION
    Marta Filizola; Fiscal Year: 2010
    ..Inferences from these studies are expected to provide new insights into the mechanisms underlying opioid-receptor function, with the ultimate goal of helping drug design. ..
  2. OPIOID RECEPTOR OLIGOMERIZATION: PREDICTION & VALIDATION
    Marta Filizola; Fiscal Year: 2006
    ..Inferences from these studies are expected to provide new insights into the mechanisms underlying opioid-receptor function, with the ultimate goal of helping drug design. ..
  3. OPIOID RECEPTOR OLIGOMERIZATION: PREDICTION & VALIDATION
    Marta Filizola; Fiscal Year: 2007
    ..Inferences from these studies are expected to provide new insights into the mechanisms underlying opioid-receptor function, with the ultimate goal of helping drug design. ..
  4. OPIOID RECEPTOR OLIGOMERIZATION: PREDICTION & VALIDATION
    Marta Filizola; Fiscal Year: 2009
    ..Inferences from these studies are expected to provide new insights into the mechanisms underlying opioid-receptor function, with the ultimate goal of helping drug design. ..