134. Kleywegt GJ, Jones TA (1994) Detection, delineation, measurement and display of cavities
in macromolecular structures. Acta Crystallogr Sect D: Biol Crystallogr 50:178–185
135. Jacoby E, Fauchère J-L, Raimbaud E et al (1999) A three binding site hypothesis for the
interaction of ligands with monoamine g protein-coupled receptors: implications for
combinatorial ligand design. Mol Inform 18:561–572
136. Deganutti G, Moro S (2017) Estimation of kinetic and thermodynamic ligand-binding
parameters using computational strategies. Future Med Chem 9:507–523
137. Chiu SH, Xie L (2016) Toward high-throughput predictive modeling of protein binding/
unbinding kinetics. J Chem Inf Model 56:1164–1174
138. Singh A (2014) Selectivity and specificity profiling of binding sites of SER/THR kinases:
case study of homo sapiens and Plasmodium falciparum. Jawaharlal Nehru University
139. Hanks SK, Hunter T (1995) Protein kinases 6. The eukaryotic protein kinase superfamily:
kinase (catalytic) domain structure and classification. FASEB J 9:576–596. https://doi.org/
10.1096/fasebj.9.8.776834
140. Freire E (2015) The binding thermodynamics of drug candidates. In: thermodynamics and
kinetics of drug binding. Wiley Online Library, pp 1–13
141. Cross S, Baroni M, Carosati E et al (2010) FLAP: GRID molecular interaction fields in
virtual screening. Validation using the DUD data set. J Chem Inf Model 50:1442–1450
142. Kaalia R, Kumar A, Srinivasan A, Ghosh I (2015) An ab initio method for designing
multi-target specific pharmacophores using complementary interaction field of aspartic
proteases. Mol Inform 34:380–393
143. Nakashima R, Sakurai K, Yamasaki S et al (2013) Structural basis for the inhibition of
bacterial multidrug exporters. Nature 500:102
144. Koshland DE (1958) Application of a theory of enzyme specificity to protein synthesis. Proc
Natl Acad Sci 44:98–104. https://doi.org/10.1073/pnas.44.2.98
145. Debler EW, Müller R, Hilvert D, Wilson IA (2008) Conformational isomerism can limit
antibody catalysis. J Biol Chem 283:16554–16560. https://doi.org/10.1074/jbc.m710256200
146. Doshi U, McGowan LC, Ladani ST, Hamelberg D (2012) Resolving the complex role of
enzyme conformational dynamics in catalytic function. Proc Natl Acad Sci 109:5699–5704.
https://doi.org/10.1073/pnas.1117060109
147. Teague SJ (2003) Implications of protein flexibility for drug discovery. Nat Rev Drug
Discov 2:527–541. https://doi.org/10.1038/nrd1129
148. Hawkins PCD (2017) Conformation generation: the state of the art. J Chem Inf Model
57:1747–1756. https://doi.org/10.1021/acs.jcim.7b00221
149. Grinter SZ, Zou X (2014) Challenges, applications, and recent advances of protein-ligand
docking in structure-based drug design. Molecules 19:10150–10176. https://doi.org/10.
3390/molecules190710150
150. Mobley DL, Dill KA (2009) Binding of small-molecule ligands to proteins: “what you see”
is not always “what you get.” Structure 17:489–498
151. London N, Movshovitz-Attias D, Schueler-Furman O (2010) The structural basis of
peptide-protein binding strategies. Structure 18:188–199. https://doi.org/10.1016/j.str.2009.
11.012
152. London N, Raveh B, Schueler-Furman O (2013) Peptide docking and structure-based
characterization of peptide binding: from knowledge to know-how. Curr Opin Struct Biol
23:894–902. https://doi.org/10.1016/j.sbi.2013.07.006
153. Bernetti M, Cavalli A, Mollica L (2017) Protein–ligand (un)binding kinetics as a new
paradigm for drug discovery at the crossroad between experiments and modelling. Med
Chem Commun 8:534–550. https://doi.org/10.1039/c6md00581k
154. Pan AC, Borhani DW, Dror RO, Shaw DE (2013) Molecular determinants of drug-receptor
binding kinetics. Drug Discov Today 18:667–673. https://doi.org/10.1016/j.drudis.2013.02.
007
155. Case DA (1988) Dynamical simulation of rate constants in protein-ligand interactions. Prog
Biophys Mol Biol 52:39–70. https://doi.org/10.1016/0079-6107(88)90007-7
168
S. K. Panday and I. Ghosh
in macromolecular structures. Acta Crystallogr Sect D: Biol Crystallogr 50:178–185
135. Jacoby E, Fauchère J-L, Raimbaud E et al (1999) A three binding site hypothesis for the
interaction of ligands with monoamine g protein-coupled receptors: implications for
combinatorial ligand design. Mol Inform 18:561–572
136. Deganutti G, Moro S (2017) Estimation of kinetic and thermodynamic ligand-binding
parameters using computational strategies. Future Med Chem 9:507–523
137. Chiu SH, Xie L (2016) Toward high-throughput predictive modeling of protein binding/
unbinding kinetics. J Chem Inf Model 56:1164–1174
138. Singh A (2014) Selectivity and specificity profiling of binding sites of SER/THR kinases:
case study of homo sapiens and Plasmodium falciparum. Jawaharlal Nehru University
139. Hanks SK, Hunter T (1995) Protein kinases 6. The eukaryotic protein kinase superfamily:
kinase (catalytic) domain structure and classification. FASEB J 9:576–596. https://doi.org/
10.1096/fasebj.9.8.776834
140. Freire E (2015) The binding thermodynamics of drug candidates. In: thermodynamics and
kinetics of drug binding. Wiley Online Library, pp 1–13
141. Cross S, Baroni M, Carosati E et al (2010) FLAP: GRID molecular interaction fields in
virtual screening. Validation using the DUD data set. J Chem Inf Model 50:1442–1450
142. Kaalia R, Kumar A, Srinivasan A, Ghosh I (2015) An ab initio method for designing
multi-target specific pharmacophores using complementary interaction field of aspartic
proteases. Mol Inform 34:380–393
143. Nakashima R, Sakurai K, Yamasaki S et al (2013) Structural basis for the inhibition of
bacterial multidrug exporters. Nature 500:102
144. Koshland DE (1958) Application of a theory of enzyme specificity to protein synthesis. Proc
Natl Acad Sci 44:98–104. https://doi.org/10.1073/pnas.44.2.98
145. Debler EW, Müller R, Hilvert D, Wilson IA (2008) Conformational isomerism can limit
antibody catalysis. J Biol Chem 283:16554–16560. https://doi.org/10.1074/jbc.m710256200
146. Doshi U, McGowan LC, Ladani ST, Hamelberg D (2012) Resolving the complex role of
enzyme conformational dynamics in catalytic function. Proc Natl Acad Sci 109:5699–5704.
https://doi.org/10.1073/pnas.1117060109
147. Teague SJ (2003) Implications of protein flexibility for drug discovery. Nat Rev Drug
Discov 2:527–541. https://doi.org/10.1038/nrd1129
148. Hawkins PCD (2017) Conformation generation: the state of the art. J Chem Inf Model
57:1747–1756. https://doi.org/10.1021/acs.jcim.7b00221
149. Grinter SZ, Zou X (2014) Challenges, applications, and recent advances of protein-ligand
docking in structure-based drug design. Molecules 19:10150–10176. https://doi.org/10.
3390/molecules190710150
150. Mobley DL, Dill KA (2009) Binding of small-molecule ligands to proteins: “what you see”
is not always “what you get.” Structure 17:489–498
151. London N, Movshovitz-Attias D, Schueler-Furman O (2010) The structural basis of
peptide-protein binding strategies. Structure 18:188–199. https://doi.org/10.1016/j.str.2009.
11.012
152. London N, Raveh B, Schueler-Furman O (2013) Peptide docking and structure-based
characterization of peptide binding: from knowledge to know-how. Curr Opin Struct Biol
23:894–902. https://doi.org/10.1016/j.sbi.2013.07.006
153. Bernetti M, Cavalli A, Mollica L (2017) Protein–ligand (un)binding kinetics as a new
paradigm for drug discovery at the crossroad between experiments and modelling. Med
Chem Commun 8:534–550. https://doi.org/10.1039/c6md00581k
154. Pan AC, Borhani DW, Dror RO, Shaw DE (2013) Molecular determinants of drug-receptor
binding kinetics. Drug Discov Today 18:667–673. https://doi.org/10.1016/j.drudis.2013.02.
007
155. Case DA (1988) Dynamical simulation of rate constants in protein-ligand interactions. Prog
Biophys Mol Biol 52:39–70. https://doi.org/10.1016/0079-6107(88)90007-7
168
S. K. Panday and I. Ghosh