A new computat
ional approach to calculat
ing b
ind
ing energ
ies and spat
ial pos
it
ions of small molecules, pept
ides, and prote
ins
in the l
ip
id b
ilayer has been developed. The method comb
ines an an
isotrop
ic solvent representat
ion of the l
ip
id b
ilayer and un
iversal solvat
ion model, wh
ich pred
icts transfer energ
ies of molecules from water to an arb
itrary med
ium w
ith def
ined polar
ity propert
ies. The un
iversal solvat
ion model accounts for hydrophob
ic, van der Waals, hydrogen-bond
ing, and electrostat
ic solute鈭抯olvent
interact
ions. The l
ip
id b
ilayer
is represented as a flu
id an
isotrop
ic env
ironment descr
ibed by prof
iles of d
ielectr
ic constant (蔚), solvatochrom
ic d
ipolar
ity parameter (蟺*), and hydrogen bond
ing ac
id
ity and bas
ic
ity parameters (伪 and 尾). The polar
ity prof
iles were calculated us
ing publ
ished d
istr
ibut
ions of quas
i-molecular segments of l
ip
ids determ
ined by neutron and X-ray scatter
ing for DOPC b
ilayer and sp
in-label
ing data that def
ine concentrat
ion of water
in the l
ip
id acyl cha
in reg
ion. The model also accounts for the preferent
ial solvat
ion of charges and polar groups by water and
includes the effect of the hydrophob
ic m
ismatch for transmembrane prote
ins. The method was tested on calculat
ions of b
ind
ing energ
ies and preferent
ial pos
it
ions
in membranes for small-molecules, pept
ides and per
ipheral membrane prote
ins that have been exper
imentally stud
ied. The new theoret
ical approach was
implemented
in a new vers
ion (2.0) of our PPM program and appl
ied for the large-scale calculat
ions of spat
ial pos
it
ions
in membranes of more than 1000 per
ipheral and
integral prote
ins. The results of calculat
ions are depos
ited
in the updated OPM database (
ich.edu" class="extLink">http://opm.phar.umich.edu).