39. Lukoyanova N, Kondos SC, Farabella I et al
(2015) Conformational changes during pore
formation by the Perforin-related protein
Pleurotolysin. PLoS Biol 13:e1002049
40. Chen Z, Chapman MS (2001) Conformational
disorder of proteins assessed by real-space
molecular dynamics refinement. Biophys J
80:1466–1472
41. Pandurangan AP, Topf M (2012) RIBFIND: a
web server for identifying rigid bodies in protein structures and to aid flexible fitting into
cryo EM maps. Bioinformatics 28:2391–2393
42. Pandurangan AP, Topf M (2012) Finding rigid
bodies in protein structures: application to flexible fitting into cryoEM maps. J Struct Biol
177:520–531
43. Zhou R, Yang G, Guo X et al (2019) Recognition of the amyloid precursor protein by
human γ-secretase. Science 363:eaaw0930
44. Yang G, Zhou R, Zhou Q et al (2019) Structural basis of notch recognition by human
γ-secretase. Nature 565:192
45. Clare DK, Vasishtan D, Stagg S et al (2012)
ATP-triggered conformational changes delineate substrate-binding and -folding mechanics
of the GroEL Chaperonin. Cell 149:113–123
46. Trabuco LG, Villa E, Mitra K et al (2008)
Flexible fitting of atomic structures into Electron microscopy maps using molecular dynamics. Structure 16:673–683
47. Trabuco LG, Villa E, Schreiner E et al (2009)
Molecular dynamics flexible fitting: a practical
guide to combine cryo-electron microscopy
and
X-ray
crystallography.
Methods
49:174–180
48. Alford RF, Leaver-Fay A, Jeliazkov JR et al
(2017) The Rosetta all-atom energy function
for macromolecular modeling and design. J
Chem Theory Comput 13:3031–3048
49. DiMaio F, Tyka MD, Baker ML et al (2009)
Refinement of protein structures into
low-resolution density maps using Rosetta. J
Mol Biol 392:181–190
50. Tama F, Miyashita O, Brooks CL III (2004)
Normal mode based flexible fitting of highresolution structure into low-resolution experimental data from cryo-EM. J Struct Biol
147:315–326
51. Lope ´z-Blanco JR, Chaco ´n P (2013) iMODFIT: efficient and robust flexible fitting based
on vibrational analysis in internal coordinates. J
Struct Biol 184:261–270
52. Ahmed A, Whitford PC, Sanbonmatsu KY et al
(2012) Consensus among flexible fitting
approaches improves the interpretation of
cryo-EM data. J Struct Biol 177:561–570
53. Pandurangan AP, Shakeel S, Butcher SJ et al
(2014) Combined approaches to flexible fitting
and assessment in virus capsids undergoing
conformational change. J Struct Biol
185:427–439
54. Newcombe J, Chatzidaki A, Sheppard TD et al
(2018) Diversity of nicotinic acetylcholine
receptor positive allosteric modulators revealed
by mutagenesis and a revised structural model.
Mol Pharmacol 93:128–140
55. Locke J, Joseph AP, Pen ˜a A et al (2017) Structural basis of human kinesin-8 function and
inhibition. Proc Natl Acad Sci 114:
E9539–E9548
56. Canutescu AA, Dunbrack RL (2003) Cyclic
coordinate descent: a robotics algorithm for
protein loop closure. Protein Sci 12:963–972
57. Wang C, Bradley P, Baker D (2007) Protein–protein docking with backbone flexibility. J
Mol Biol 373:503–519
58. Mandell DJ, Coutsias EA, Kortemme T (2009)
Sub-angstrom accuracy in protein loop reconstruction by robotics-inspired conformational
sampling. Nat Methods 6:551–552
59. Scaiola A, Leibundgut M, Boehringer D et al
(2019) Structural basis of translation inhibition
by cadazolid, a novel quinoxolidinone antibiotic. Sci Rep 9:5634
60. Verdonk ML, Cole JC, Hartshorn MJ et al
(2003) Improved protein–ligand docking
using GOLD. Proteins Struct Funct Bioinforma 52:609–623
61. Dominguez C, Boelens R, Bonvin AMJJ
(2003) HADDOCK: a proteinÀprotein docking approach based on biochemical or biophysical information. J Am Chem Soc
125:1731–1737
62. Wang Z, Sun H, Yao X et al (2016) Comprehensive evaluation of ten docking programs on
a diverse set of protein–ligand complexes: the
prediction accuracy of sampling power and
scoring power. Phys Chem Chem Phys
18:12964–12975
63. Houston DR, Walkinshaw MD (2013) Consensus docking: improving the reliability of
docking in a virtual screening context. J
Chem Inf Model 53:384–390
64. Catarinella M, Gru ¨ner T, Strittmatter T et al
(2009) BTB-1: a small molecule inhibitor of
the mitotic motor protein Kif18A. Angew
Chem Int Ed 48:9072–9076
65. Kucukelbir A, Sigworth FJ, Tagare HD (2014)
Quantifying the local resolution of cryo-EM
density maps. Nat Methods 11:63–65
66. Shen M, Sali A (2006) Statistical potential for
assessment and prediction of protein structures. Protein Sci 15:2507–2524
222
Tristan Cragnolini et al.
(2015) Conformational changes during pore
formation by the Perforin-related protein
Pleurotolysin. PLoS Biol 13:e1002049
40. Chen Z, Chapman MS (2001) Conformational
disorder of proteins assessed by real-space
molecular dynamics refinement. Biophys J
80:1466–1472
41. Pandurangan AP, Topf M (2012) RIBFIND: a
web server for identifying rigid bodies in protein structures and to aid flexible fitting into
cryo EM maps. Bioinformatics 28:2391–2393
42. Pandurangan AP, Topf M (2012) Finding rigid
bodies in protein structures: application to flexible fitting into cryoEM maps. J Struct Biol
177:520–531
43. Zhou R, Yang G, Guo X et al (2019) Recognition of the amyloid precursor protein by
human γ-secretase. Science 363:eaaw0930
44. Yang G, Zhou R, Zhou Q et al (2019) Structural basis of notch recognition by human
γ-secretase. Nature 565:192
45. Clare DK, Vasishtan D, Stagg S et al (2012)
ATP-triggered conformational changes delineate substrate-binding and -folding mechanics
of the GroEL Chaperonin. Cell 149:113–123
46. Trabuco LG, Villa E, Mitra K et al (2008)
Flexible fitting of atomic structures into Electron microscopy maps using molecular dynamics. Structure 16:673–683
47. Trabuco LG, Villa E, Schreiner E et al (2009)
Molecular dynamics flexible fitting: a practical
guide to combine cryo-electron microscopy
and
X-ray
crystallography.
Methods
49:174–180
48. Alford RF, Leaver-Fay A, Jeliazkov JR et al
(2017) The Rosetta all-atom energy function
for macromolecular modeling and design. J
Chem Theory Comput 13:3031–3048
49. DiMaio F, Tyka MD, Baker ML et al (2009)
Refinement of protein structures into
low-resolution density maps using Rosetta. J
Mol Biol 392:181–190
50. Tama F, Miyashita O, Brooks CL III (2004)
Normal mode based flexible fitting of highresolution structure into low-resolution experimental data from cryo-EM. J Struct Biol
147:315–326
51. Lope ´z-Blanco JR, Chaco ´n P (2013) iMODFIT: efficient and robust flexible fitting based
on vibrational analysis in internal coordinates. J
Struct Biol 184:261–270
52. Ahmed A, Whitford PC, Sanbonmatsu KY et al
(2012) Consensus among flexible fitting
approaches improves the interpretation of
cryo-EM data. J Struct Biol 177:561–570
53. Pandurangan AP, Shakeel S, Butcher SJ et al
(2014) Combined approaches to flexible fitting
and assessment in virus capsids undergoing
conformational change. J Struct Biol
185:427–439
54. Newcombe J, Chatzidaki A, Sheppard TD et al
(2018) Diversity of nicotinic acetylcholine
receptor positive allosteric modulators revealed
by mutagenesis and a revised structural model.
Mol Pharmacol 93:128–140
55. Locke J, Joseph AP, Pen ˜a A et al (2017) Structural basis of human kinesin-8 function and
inhibition. Proc Natl Acad Sci 114:
E9539–E9548
56. Canutescu AA, Dunbrack RL (2003) Cyclic
coordinate descent: a robotics algorithm for
protein loop closure. Protein Sci 12:963–972
57. Wang C, Bradley P, Baker D (2007) Protein–protein docking with backbone flexibility. J
Mol Biol 373:503–519
58. Mandell DJ, Coutsias EA, Kortemme T (2009)
Sub-angstrom accuracy in protein loop reconstruction by robotics-inspired conformational
sampling. Nat Methods 6:551–552
59. Scaiola A, Leibundgut M, Boehringer D et al
(2019) Structural basis of translation inhibition
by cadazolid, a novel quinoxolidinone antibiotic. Sci Rep 9:5634
60. Verdonk ML, Cole JC, Hartshorn MJ et al
(2003) Improved protein–ligand docking
using GOLD. Proteins Struct Funct Bioinforma 52:609–623
61. Dominguez C, Boelens R, Bonvin AMJJ
(2003) HADDOCK: a proteinÀprotein docking approach based on biochemical or biophysical information. J Am Chem Soc
125:1731–1737
62. Wang Z, Sun H, Yao X et al (2016) Comprehensive evaluation of ten docking programs on
a diverse set of protein–ligand complexes: the
prediction accuracy of sampling power and
scoring power. Phys Chem Chem Phys
18:12964–12975
63. Houston DR, Walkinshaw MD (2013) Consensus docking: improving the reliability of
docking in a virtual screening context. J
Chem Inf Model 53:384–390
64. Catarinella M, Gru ¨ner T, Strittmatter T et al
(2009) BTB-1: a small molecule inhibitor of
the mitotic motor protein Kif18A. Angew
Chem Int Ed 48:9072–9076
65. Kucukelbir A, Sigworth FJ, Tagare HD (2014)
Quantifying the local resolution of cryo-EM
density maps. Nat Methods 11:63–65
66. Shen M, Sali A (2006) Statistical potential for
assessment and prediction of protein structures. Protein Sci 15:2507–2524
222
Tristan Cragnolini et al.