Table 1:

Model definitions and corresponding metrics. Among models reported in the literature are models Ml through M6 (empirical models) and the model M7 (a fractional population model). For models reported in this work, M8 is an empirical model and M9 is a fractional population model. Additional details on models M8 and M9 are provided in supporting information.

	criteria
Model	1	2	3	4	5	6	7	8	Protection Factor Definitions
M1ref.55	✔	✔							log$(P{F}_i)=$ u * (SAi)+ v/(HBi)
M2ref.38	✔		✔						ln$(P{F}_i)=\left({\beta }_c{N}_i^c+{\beta }_h{N}_i^h\right)$
M3ref.39	✔			✔					ln$(P{F}_i)=\left({\beta }_c{N}_i^c+{\beta }_h{N}_i^h\right)$
M4ref.40			✔		✔				ln$(P{F}_i)=\left({\beta }_c{N}_i^c+{\beta }_r{\left(N_i^r\right)}^{-1}\right)$
M5ref.42	✔								$(P{F}_i)=\left(C_{o}N{H}_i^{sol}+C_{c}N{H}_i^{\beta }\right)/C_{o}N{H}_i^{sol}$
M6ref.29	✔								$(P{F}_i)=base/\left(1+{(\sqrt{base})}^{1-NHsta{t}_i}\right)$
M7ref.30						✔	✔		$(P{F}_i)=$${\tau }_C/{\tau }_O$
M8†							✔	✔	ln$(P{F}_i)=\left({\beta }_{s}SAS{A}_i^{-{\gamma }_s}+{\beta }_p{D}_i^{-{\gamma }_p}\right)$
M9†							✔	✔	PFi$={\tau }_C/{\tau }_O$

¹Hydrogen bond;

²Distance from the surface;

³# of residues in the vicinity;

⁴# of heavy atoms in the vicinity;

⁵RMSF;

⁶# of waters in the vicinity;

⁷polar atoms in the vicinity;

⁸SASA;

^†new model proposed in this work.