nonequilibrium measurements using
maximum-likelihood methods. Phys Rev Lett
91(14):140601
- Shirts MR, Chodera JD (2008) Statistically
optimal analysis of samples from multiple equi-
librium states. J Chem Phys 129:124105
- Paliwal H, Shirts MR (2011) A benchmark test
set for alchemical free energy transformations
and its use to quantify error in common free
energy methods. J Chem Theory Comput 7
(12):4115–4134
- Abraham MJ, Murtola T, Schulz R, Pa ́ll S,
Smith JC, Hess B, Lindahl E (2015) GRO-
MACS: high performance molecular simula-
tions through multi-level parallelism from
laptops to supercomputers. SoftwareX
1–2:19–25
- Homeyer N, Gohlke H (2013) FEW: a work-
flow tool for free energy calculations of ligand
binding. J Comput Chem 34(11):965–973
- Liu P, Dehez F, Cai W, Chipot C (2012) A
toolkit for the analysis of free-energy perturba-
tion calculations. J Chem Theory Comput 8
(8):2606–2616
- Pham TT, Shirts MR (2011) Identifying low
variance pathways for free energy calculations
of molecular transformations in solution phase.
J Chem Phys 135(3):034114
- Klimovich P, Shirts M, Mobley D (2015)
Guidelines for the analysis of free energy calcu-
lations. J Comput Aided Mol Des 29
(5):397–411
- Case DA, Betz RM, Cerutti DS, Cheatham TE
III, Darden TA, Duke RE, Giese TJ, Gohlke H,
Goetz AW, Homeyer N, Izadi S, Janowski P,
Kaus J, Kovalenko A, Lee TS, LeGrand S, Li P,
Lin C, Luchko T, Luo R, Madej BD,
Mermelstein D, Merz KM, Monard G,
Nguyen H, Nguyen HT, Omelyan I,
Onufriev A, Roe DR, Roitberg A, Sagui C,
Simmerling CL, Botello-Smith WM, Swails J,
Walker RC, Wang J, Wolf RM, Wu X, Xiao L,
Kollman PA (2016) AMBER 2016. University
of California, San Francisco
- Boresch S, Tettinger F, Leitgeb M, Karplus M
(2003) Absolute binding free energies: a quan-
titative approach for their calculation. J Phys
Chem B 107(35):9535–9551
- Mobley DL, Chodera JD, Dill KA (2006) On
the use of orientational restraints and symme-
try corrections in alchemical free energy calcu-
lations. J Chem Phys 125(8):084902
- Evoli S, Mobley DL, Guzzi R, Rizzuti B
(2016) Multiple binding modes of ibuprofen
in human serum albumin identified by absolute
binding free energy calculations. Phys Chem
Chem Phys 18(47):32358–32368
35. Cappel D, Hall ML, Lenselink EB, Beuming T,
Qi J, Bradner J, Sherman W (2016) Relative
binding free energy calculations applied to pro-
tein homology models. J Chem Inf Model 56
(12):2388–2400
36. Mobley DL, Graves AP, Chodera JD, McRey-
nolds AC, Shoichet BK, Dill KA (2007) Pre-
dicting absolute ligand binding free energies to
a simple model site. J Mol Biol 371
(4):1118–1134
37. Mobley DL (2012) Let’s get honest about
sampling. J Comput Aided Mol Des 26
(1):93–95
38. Mobley DL, Klimovich PV (2012) Perspective:
alchemical free energy calculations for drug
discovery. J Chem Phys 137(23):230901
39. Phillips JC, Braun R, Wang W, Gumbart J,
Tajkhorshid E, Villa E, Chipot C, Skeel RD,
Kale L, Schulten K (2005) Scalable molecular
dynamics with NAMD. J Comput Chem
26:1781–1802
40. Hornak V, Abel R, Okur A, Strockbine B,
Roitberg A, Simmerling C (2006) Comparison
of multiple Amber force fields and develop-
ment of improved protein backbone para-
meters. Proteins 65(3):712–725
41. Lindorff-Larsen K, Piana S, Palmo K,
Maragakis P, Klepeis J, Dror R, Shaw D
(2010) Improved side-chain torsion potentials
for the Amber ff99SB protein force field. Pro-
teins 78:1950–1958
42. Maier JA, Martinez C, Kasavajhala K,
Wickstrom L, Hauser KE, Simmerling C
(2015) ff14SB: improving the accuracy of pro-
tein side chain and backbone parameters from
ff99SB. J Chem Theory Comput 11
(8):3696–3713
43. MacKerell AD, Bashford D, Bellott M, Dun-
brack RL, Evanseck JD, Field MJ, Fischer S,
Gao J, Guo H, Ha S, Joseph-McCarthy D,
Kuchnir L, Kuczera K, Lau FTK, Mattos C,
Michnick S, Ngo T, Nguyen DT, Prodhom B,
Reiher WE, Roux B, Schlenkrich M, Smith JC,
Stote R, Straub J, Watanabe M, Wio ́rkiewicz-
Kuczera J, Yin D, Karplus M (1998) All-atom
empirical potential for molecular modeling and
dynamics studies of proteins. J Phys Chem B
102(18):3586–3616
44. Mackerell AD (2004) Empirical force fields for
biological macromolecules: overview and
issues. J Comput Chem 25(13):1584–1604
45. Best RB, Zhu X, Shim J, Lopes PEM, Mittal J,
Feig M, MacKerell AD (2012) Optimization of
the additive CHARMM all-atom protein force
field targeting improved sampling of the back-
bone φ, ψ and side-chain χ(1) and
Absolute Alchemical Free Energy 229
