Alexander D. MacKerell

Tyr66 acts as a conformational switch in the closed-to-open transition of the SHP-2 N-SH2-domain phosphotyrosine-peptide binding cleft (2007)

Guvench, Olgun, Qu, Cheng-Kui, MacKerell, Alexander D

Abstract Background The N-terminal SH2 domain (N-SH2) of the non-receptor tyrosine phosphatase SHP-2 is involved both in localization of SHP-2 by recognition of phosphotyrosine (pY) peptides and...

Tyr66 acts as a conformational switch in the closed-to-open transition of the SHP-2 N-SH2-domain phosphotyrosine-peptide binding cleft (2007)

Guvench, Olgun, Qu, Cheng-Kui, MacKerell, Alexander D

Abstract Background The N-terminal SH2 domain (N-SH2) of the non-receptor tyrosine phosphatase SHP-2 is involved both in localization of SHP-2 by recognition of phosphotyrosine (pY) peptides and...

Tyr66 acts as a conformational switch in the closed-to-open transition of the SHP-2 N-SH2-domain phosphotyrosine-peptide binding cleft. (2007)

Guvench, Olgun, Qu, Cheng-Kui, MacKerell, Alexander D

BACKGROUND: The N-terminal SH2 domain (N-SH2) of the non-receptor tyrosine phosphatase SHP-2 is involved both in localization of SHP-2 by recognition of phosphotyrosine (pY) peptides and...

Importance of the CMAP correction to the CHARMM22 protein force field: dynamics of hen lysozyme. (2006)

Buck, Matthias, Bouguet-Bonnet, Sabine, Pastor, Richard W., MacKerell, Alexander D.

The recently developed CMAP correction to the CHARMM22 force field (C22) is evaluated from 25 ns molecular dynamics simulations on hen lysozyme. Substantial deviations from experimental backbone root...

Cooperative binding of DNA and CBF{beta} to the Runt domain of the CBF{alpha} studied via MD simulations (2005)

Habtemariam, Bahru, Anisimov, Victor M., MacKerell, Alexander D.

The Runt domain (RD) is the DNA-binding region of the Runx genes. A related protein, known as core binding factor β (CBFβ) also binds to the RD to enhance RD–DNA interaction by 6- to 10-fold....

Caught in the act: visualization of an intermediate in the DNA base-flipping pathway induced by HhaI methyltransferase (2004)

Horton, John R., Ratner, Gary, Banavali, Nilesh K., Huang, Niu, Choi, Yongseok, Maier, Martin A., ...

Rotation of a DNA or RNA nucleotide out of the double helix and into a protein pocket (‘base flipping’) is a mechanistic feature common to some DNA/RNA-binding proteins. Here, we report the...

Altered structural fluctuations in duplex RNA versus DNA: a conformational switch involving base pair opening (2003)

Pan, Yongping, MacKerell, Alexander D.

DNA and RNA are known to have different structural properties. In the present study, molecular dynamics (MD) simulations on a series of RNA and DNA duplexes indicate differential structural...

Re-examination of the intrinsic, dynamic and hydration properties of phosphoramidate DNA (2001)

Banavali, Nilesh K., MacKerell, Alexander D.

Intrinsic energetic and solvation factors contributing to the unusual structural and biochemical properties of N3′-phosphoramidate DNA analogs have been re-examined using a combination of quantum...

New insights into the structure of abasic DNA from molecular dynamics simulations (2000)

Barsky, Daniel, Foloppe, Nicolas, Ahmadia, Sarah, Wilson III, David M., MacKerell, Alexander D.

Abasic (AP) sites constitute a common form of DNA damage, arising from the spontaneous or enzymatic breakage of the N-glycosyl bond and the loss of a nucleotide base. To examine the effects of such...

Re-examination of the intrinsic, dynamic and hydration properties of phosphoramidate DNA

Banavali, Nilesh K., MacKerell, Alexander D.

Intrinsic energetic and solvation factors contributing to the unusual structural and biochemical properties of N3′-phosphoramidate DNA analogs have been re-examined using a combination of quantum...

New insights into the structure of abasic DNA from molecular dynamics simulations

Barsky, Daniel, Foloppe, Nicolas, Ahmadia, Sarah, Wilson, David M., MacKerell, Alexander D.

Abasic (AP) sites constitute a common form of DNA damage, arising from the spontaneous or enzymatic breakage of the N-glycosyl bond and the loss of a nucleotide base. To examine the effects of such...

Protein-facilitated base flipping in DNA by cytosine-5-methyltransferase

Huang, Niu, Banavali, Nilesh K., MacKerell, Alexander D.

DNA methylation, various DNA repair mechanisms, and possibly early events in the opening of DNA as required for transcription and replication are initiated by flipping of a DNA base out of the DNA...

Altered structural fluctuations in duplex RNA versus DNA: a conformational switch involving base pair opening

Pan, Yongping, MacKerell, Alexander D.

DNA and RNA are known to have different structural properties. In the present study, molecular dynamics (MD) simulations on a series of RNA and DNA duplexes indicate differential structural...

Caught in the act: visualization of an intermediate in the DNA base-flipping pathway induced by HhaI methyltransferase

Horton, John R., Ratner, Gary, Banavali, Nilesh K., Huang, Niu, Choi, Yongseok, Maier, Martin A., ...

Rotation of a DNA or RNA nucleotide out of the double helix and into a protein pocket (‘base flipping’) is a mechanistic feature common to some DNA/RNA-binding proteins. Here, we report the...

Cooperative binding of DNA and CBFβ to the Runt domain of the CBFα studied via MD simulations

Habtemariam, Bahru, Anisimov, Victor M., MacKerell, Alexander D.

The Runt domain (RD) is the DNA-binding region of the Runx genes. A related protein, known as core binding factor β (CBFβ) also binds to the RD to enhance RD–DNA interaction by 6- to 10-fold....

Intrinsic conformational energetics associated with the glycosyl torsion in DNA: a quantum mechanical study.

Foloppe, Nicolas, Hartmann, Brigitte, Nilsson, Lennart, MacKerell, Alexander D

The glycosyl torsion (chi) in nucleic acids has long been recognized to be a major determinant of their conformational properties. chi torsional energetics were systematically mapped in...

Re-examination of the intrinsic, dynamic and hydration properties of phosphoramidate DNA

Banavali, Nilesh K., MacKerell, Alexander D.

Intrinsic energetic and solvation factors contributing to the unusual structural and biochemical properties of N3′-phosphoramidate DNA analogs have been re-examined using a combination of quantum...

New insights into the structure of abasic DNA from molecular dynamics simulations

Barsky, Daniel, Foloppe, Nicolas, Ahmadia, Sarah, Wilson, David M., MacKerell, Alexander D.

Abasic (AP) sites constitute a common form of DNA damage, arising from the spontaneous or enzymatic breakage of the N-glycosyl bond and the loss of a nucleotide base. To examine the effects of such...

Protein-facilitated base flipping in DNA by cytosine-5-methyltransferase

Huang, Niu, Banavali, Nilesh K., MacKerell, Alexander D.

DNA methylation, various DNA repair mechanisms, and possibly early events in the opening of DNA as required for transcription and replication are initiated by flipping of a DNA base out of the DNA...

Altered structural fluctuations in duplex RNA versus DNA: a conformational switch involving base pair opening

Pan, Yongping, MacKerell, Alexander D.

DNA and RNA are known to have different structural properties. In the present study, molecular dynamics (MD) simulations on a series of RNA and DNA duplexes indicate differential structural...

Caught in the act: visualization of an intermediate in the DNA base-flipping pathway induced by HhaI methyltransferase

Horton, John R., Ratner, Gary, Banavali, Nilesh K., Huang, Niu, Choi, Yongseok, Maier, Martin A., ...

Rotation of a DNA or RNA nucleotide out of the double helix and into a protein pocket (‘base flipping’) is a mechanistic feature common to some DNA/RNA-binding proteins. Here, we report the...

Cooperative binding of DNA and CBFβ to the Runt domain of the CBFα studied via MD simulations

Habtemariam, Bahru, Anisimov, Victor M., MacKerell, Alexander D.

The Runt domain (RD) is the DNA-binding region of the Runx genes. A related protein, known as core binding factor β (CBFβ) also binds to the RD to enhance RD–DNA interaction by 6- to 10-fold....

Intrinsic conformational energetics associated with the glycosyl torsion in DNA: a quantum mechanical study.

Foloppe, Nicolas, Hartmann, Brigitte, Nilsson, Lennart, MacKerell, Alexander D

The glycosyl torsion (chi) in nucleic acids has long been recognized to be a major determinant of their conformational properties. chi torsional energetics were systematically mapped in...

Importance of the CMAP Correction to the CHARMM22 Protein Force Field: Dynamics of Hen Lysozyme

Buck, Matthias, Bouguet-Bonnet, Sabine, Pastor, Richard W., MacKerell, Alexander D.

The recently developed CMAP correction to the CHARMM22 force field (C22) is evaluated from 25 ns molecular dynamics simulations on hen lysozyme. Substantial deviations from experimental backbone root...

Ab Initio Modeling of Glycosyl Torsions and Anomeric Effects in a Model Carbohydrate: 2-Ethoxy Tetrahydropyran

Woodcock, H. Lee, Moran, Damian, Pastor, Richard W., MacKerell, Alexander D., Brooks, Bernard R.

A range of ab initio calculations were carried out on the axial and equatorial anomers of the model carbohydrate 2-ethoxy tetrahydropyran to evaluate the level of theory required to accurately...

Is Arginine Charged in a Membrane?

Li, Libo, Vorobyov, Igor, MacKerell, Alexander D., Allen, Toby W.

“Charged” amino acids play countless important roles in protein structure and function. Yet when these side chains come into contact with membranes we do not fully understand their behavior. This...

Using Caenorhabditis elegans as a model organism for evaluating extracellular signal-regulated kinase docking domain inhibitors

Chen, Fengming, MacKerell, Alexander D., Luo, Yuan, Shapiro, Paul

We have recently identified several novel ATP-independent inhibitors that target the extracellular signal-regulated kinase-2 (ERK2) protein and inhibit substrate phosphorylation. To further...

Computational Fragment-Based Binding Site Identification by Ligand Competitive Saturation

Guvench, Olgun, MacKerell, Alexander D.

Fragment-based drug discovery using NMR and x-ray crystallographic methods has proven utility but also non-trivial time, materials, and labor costs. Current computational fragment-based approaches...

Molecular Dynamics Studies of Polyethylene Oxide and Polyethylene Glycol: Hydrodynamic Radius and Shape Anisotropy

Lee, Hwankyu, Venable, Richard M., MacKerell, Alexander D., Pastor, Richard W.

A revision (C35r) to the CHARMM ether force field is shown to reproduce experimentally observed conformational populations of dimethoxyethane. Molecular dynamics simulations of 9, 18, 27, and 36-mers...